Colostrum Research

Immune Factors


Akita EM, Li-Chan EC.  Isolation of bovine immunoglobulin G subclasses from milk, colostrum, and whey using immobilized egg yolk antibodies.  Journal of Dairy Science 81(1):54-63 (1998).  Both IgG1 and IgG2 subclasses of IgG were isolated from bovine colostrum and milk.  Removal of IgG1 and IgG2 also resulted in the removal of all IgG activity from the colostrum and milk.

PubMed Reference    PMID:9493082

Armogida, SA, Yannaras, NM, Melton, AL, Srivastava, MD.   Identification and quantification of innate immune system mediators in human breast milk.  Allergy and Asthma Proceedings 25(5):297-304 (2004).  Mediators of the innate immune system were determined in human colostrum.  Human neutrophil-derived a-defensin 1 (HNP-1) and human beta-defensin 2 (HBD-2) were present in high amounts, human alpha-defensin 6 (HD-6) was present in moderate amounts, and HD-5 and HBD-1 were present in the lowest concentrations.  HNP-1, HD-5 and HD-6 were present in significantly higher amounts in colostrum than in mature milk.  It is believed that the innate immune system provides protection for both maternal breast tissue and the developing digestive system of newborns.

PubMed Reference    PMID:15603202

Bishop GA, Haxhinasto SA, Stunz LL, Hostager BS. Antigen-specific B-lymphocyte activationCritical Reviews in Immunology 23(3):159-197 (2003).  B cells have the exclusive ability to produce and secrete immunoglobulins of various types.  They also function in antigen presentation and the production of a number of cytokines and chemokines.

PubMed Reference    PMID:14584878

Bitzan MM, Gold BD, Philpott DJ, Huesca M, Sherman PM, Karch H, Lissner R, Lingwood CA, Karmali MA. Inhibition of Helicobacter pylori and Helicobactor mustelae binding to lipid receptors by bovine colostrum. The Journal of Infectious Diseases 177(4):955-961 (1998).  H. pylori causes gastric and duodenal ulcers in humans, and H. muselae is a gastric pathogen in ferrets.  Both bind to phosphatidylethanolamine (PE), a phospholipid component of cell membranes in gastric mucosal cells.  Bovine colostrum blocks attachment of the pathogens to PE.  Colostral PE or PE derivatives also bind to the pathogens, inhibiting their ability to bind to target cells.

PubMed Reference    PMID:9534968

Bocci V, Von Bremen K, Corradeschi F, Luzzi E, Paulesu L. What is the role of cytokines in human colostrum? Journal of Biological Regulators and Homeostatic Agents. 5(4):121-124 (1991). Cytokines identified for the first time in colostrum, including interleukin (IL)-1, IL-6, interferon gamma, and tumor necrosis factor (TNF).

PubMed Reference    PMID:1725087

Boesman-Finkelsein M, Walton NE, Finkelstein RA. Bovine lactogenic immunity against cholera toxin-related enterotoxins and Vibrio cholerae outer membranes. Infection and Immunity 57(4):1227-1234 (1989). Bovine colostrum provided immunity against cholera toxins and V. cholerae outer membranes.  The immunoglobulin provided significant protection against diarrhea in baby rabbits which had been challenged intraintestinally with virulent cholera vibrios.

PubMed Reference    PMID:2925248

Boesman-Finkelstein M. and Finkelstein R. Passive oral immunisation of children. Lancet 2(8675):1336 (1989). Passive immunization children against rotavirus (main cause of diarrhea in young children) using immunoglobin from bovine colostrum.

PubMed Reference    PMID2574282

Bogstedt AK, Johansen K, Hatta H, Kim M, Casswall T, Svensson L, Hammarstrom L. Passive immunity against diarrhoea. Acta Paediatrica 85(2):125-128 (1996). Effectiveness of passive oral immunization using bovine immunoglobulin from colostrum.

PubMed Reference    PMID:8640033

Bottcher MF, Jenmalm MC, Bjorksten B.  Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants.  Pediatric Allergy and Immunology 14(1):35-41 (2003).  Human breast milk contains IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-16, interferon gamma, transforming growth factors beta 1 and beta 2, and other cytokines.  None of their levels correlated with the appearance of atopic (allergic) symptoms during the first two years of life.

PubMed Reference    PMID:12603709

Brinkmann V, Geiger T, Alkan S, Heusser CH.  Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells.  Journal of Experimental Medicine 178(5):1655-1663 (1993).  Allergic disease and chronic infections are marked by an increased ration of T helper cells type 2 (Th2), resulting in immune dysregulation.  Th2 cells produce increased levels of IL-4 and decreased levels of interferon gamma.  Interferon alpha was shown to favor the induction and maintenance of Th1 cells, counteracting Th2-driven allergic responses.

PubMed Reference    PMID:8228812

Brock JH, Ortega F, Pineiro A.  Bactericidal and hemolytic activity of complement in bovine colostrum and serum: effect of proteolytic enzymes and ethylene glycol tetraacetic acid (EGTA).  Annales d’Immunologie  126C(4):439-451 (1975).  Bovine colostrum has bactericidal activity against an enteropathic strain of E. coli.  Low but significant levels of complement in colostrum appear to be responsible for this activity, and the activity appears to be modulated by classical complement pathway rather than the alternate pathway which appears to operate in bovine serum.

PubMed Reference    PMID:813560

Bryan DL, Hawkes JS, Gibson RA.  Interleukin-12 in human milk. Pediatric Research 45(6):858-859 (1999).  IL-12 was found in human colostrum and milk.  The concentration dropped with time.

PubMed Reference    PMID:10367778

Buescher ES, McWilliams-Koeppen P.  Soluble tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk bind to TNF-alpha and neutralize TNF-alpha bioactivity.  Pediatric Research 44(1):37-42 (1998).  Tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk can bind to TNF-alpha and block its bioactivity.  This is most likely a way of modulating TNF-alpha activity in the colostrum and milk.

PubMed Reference    PMID:9667368

Casswall TH, Sarker SA, Albert MJ, Fuchs GJ, Bergstrom M, Bjorck L, Hammarstrom L. Treatment of Helicobacter pylori infection in infants in rural Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum. Alimentary Pharmacology and Therapeutics 12(6):563-568 (1998). Bangladeshi children infected with H. pylori (a principal cause of ulcers and gastrointestinal disease in children) were given immunoglobulins from hyperimmune bovine colostrum.  None became negative for H. pylori, probably because infection is very common in high endemic areas, so reinfection prevents proper evaluation of the effectiveness of the treatment.

PubMed Reference    PMID:9678817

Cesarone MR, Belcaro G, Di Renzo A, Dugall M, Cacchio M, Ruffini I, Pellegrini L, Del Boccio G, Fano F, Ledda A, Bottari A, Ricci A, Stuard S, Vinciguerra G.   Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino.  Clinical and Applied Thrombosis/Hemostasis 13(2):13-16 (2007).  Two month supplementation with oral colostrum was compared to anti-influenza vaccination in the prevention of flu.  Colostrum was at least three times more effective than vaccination in preventing flu.

PubMed Reference    PMID:17456621

Chan MC, Cheung CY, Chui WH, Tsao SW, Nicholls JM, Chan YO, Chan RW, Long HT, Poon LL, Guan Y, Peiris JS. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 6:135 (2006).  H5N1 influenza A viruses are much more potent inducers of pro-inflammatory cytokines, including IP-10, RANTES, interferon-beta, and IL-6 in human alvelolar and bronchial epithelial cells.  This hyper-induction of inflammatory cytokines is the most dangerous and lethal action of H5N1.

PubMed Reference    PMID:16283933

Collins AM, Roberton DM, Hosking CS, Flannery GR. Bovine milk, including pasteurised milk, contains antibodies directed against allergens of clinical importance to man. International Archives of Allergy and Applied Immunology 96(4):362-367 (1991). Pasteurised and raw bovine milk and bovine colostrum samples were assayed by enzyme-linked immunoassay for the presence of antibodies directed against a selection of allergens of importance in human atopic disease. Samples were tested for the presence of antibodies directed against or cross-reacting with ryegrass pollen, house dust mites, Aspergillus mould and wheat proteins. Antibodies of each specificity were detected in every sample tested.

PubMed Reference    PMID:1809694

Davidson GP, Whyte PB, Daniels E, Franklin K, Nunan H, McCloud PI, Moore AG, Moore DJ. (1989) Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet 2(8665):709-12. Children given colostral immunoglobulin against rotavirus were protected from infection during a hospital visit, while those in the control group had a high incidence of infection.

PubMed Reference    PMID:2570959

Ebina T, Sato A, Umezu K, Ishida N, Ohyama S, Ohizumi A, Aikawa K, Katagiri S, Katsushima N, Imai A. Prevention of rotavirus infection by cow colostrum containing antibody against human rotavirus. Lancet. 2(8357):1029-1030 (1983). Immunoglobulin from cows hyperimmunized against rotavirus showed good protective effects on infants exposed to rotavirus.  6 of 7 infants who received milk only came down with rotavirus-induced diarrhea, while only 1 of 6 who received the immunoglobulin did.

PubMed Reference    PMID:4069083

Eggena MP, Barugahare B, Jones N, Okello M, Mutalya S, Kityo C, Mugyenyi P, Cao H. Depletion of regulatory T cells in HIV infection is associated with immune activation.  Journal of Immunology 174(7):4407-4414 (2005).  Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate helper CD4+ T cell depletion.  Regulatory T cells actively down-regulate immune responses.  In a study using 81 Ugandan volunteers, it was found that depletion of regulatory T cells occurs at different rates than other CD4+ T cells, resulting in an increased regulator to helper ratio in many patients with advanced disease.  This skewing may contribute to T cell effector dysfunction.

PubMed Reference    PMID:15778406

Feldmann M, Brennan F, Maini R. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology 14:397-440 (1996). This study confirmed that TNF-α is the major controlling factor in the inflammatory response seen in rheumatoid arthritis.  Therefore the ability of colostrum to modulate the activity of TNF-α may be the way in which colostrum is of benefit to those suffering from rheumatoid arthritis (and other types of arthritis as well).

PubMed Reference      PMID:8717520

Feldmann M, Maini RN. The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology 38(suppl 2):3-7 (1999). The down-regulation of TNF-alpha, the cytokine that controls the inflammatory cascade of cytokines, has proven a useful therapeutic target in the treatment of rheumatoid arthritis.

PubMed Reference    PMID:10646481

Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalstieg FC, Rassin DK, Goldman AS.  Interleukin-10 in human milk.  Pediatric Research 37(4pt1):444-449 (1995).  IL-10 was found to be present in human colostrum milk up to 80 hours postpartum.

PubMed Reference    PMID:7596683

Gerson C, Sabater J, Scuri M, Torbati A, Coffey R, Abraham JW, Lauredo I, Forteza R, Wanner A, Salathe M, Abraham WM, Conner GE.  The lactoperoxidase system functions in bacterial clearance of airways.  American Journal of Respiratory Cell and Molecular Biology 22(6):665-671 (2000).  Lactoperoxidase, a component of airway mucus, is one of the principal defenses against respiratory infection.  Thiocyanate is present in the mucus in sufficient concentration for the lactoperoxidase system to be effective.  Airway lactoperoxidase forms the biocidal compound hypothiocyanate.  It is largely responsible for bacterial clearance of the airways.

PubMed Reference     PMID:10837362

Hagiwara K, Kataoka S, Yamanaka H, Kirisawa R, Iwai H.  Detection of cytokines in bovine colostrum.  Veterinary Immunology and Immunopathology 76(3-4):183-190 (2000).  ELISA specific for bovine cytokines detected five cytokines in bovine colostrum: IL-1β, IL-6, INF-α, INF-γ, and IL-1 ra (receptor antagonist).

PubMed Reference    PMID:11044552

Hagiwara K, Yamanaka H, Higuchi H, Nagahata H, Kirisawa R, Iwai H.  Oral administration of IL-1 beta enhanced the proliferation of lymphocytes and the O(2)(-) production of neutrophils in newborn calf.  Veterinary Immunology and Immunopathology 81(1-2):59-69 (2001).  Calves given labeled IL-1 beta orally showed that it was passively transferred to the calves.  The calves also showed a significant increase in white blood cell count.  IL-1 beta has an immunostimulatory effect.

PubMed Reference    PMID:11498247

Hanson LA, Ahlstedt S, Andersson B, Carlsson B, Cole MF, Cruz JR, Dahlgren U, Ericsson TH, Jalil F, Khan SR, Mellander L, Schneerson R, Eden CS, Soderstrom T, Wadsworth C. Mucosal Immunity. Annals of the New York Academy of Sciences 409:1-21 (1983). Many factors come into play in providing defense against pathogens on the mucosal membranes of the body.  These include secretory immunoglobulin A (sIgA), immunoglobulin G (IgG), and oligosaccharides (which prevent attachment of pathogens to mucosal lining cells) all play a role.  All are found in colostrum.

PubMed Reference    PMID:6191608

Hashira S, Okitsu-Negishi S, Yoshino K. Interleukin 8 in the human colostrum.  Biology of the Neonate 82(1):34-38 (2002).  Human colostrum contains IL-8.

PubMed Reference    PMID:12119539

Hazenburg MP, Klasen IS, Kool J, Ruseler-van Embden JG, Severijnen AJ. Are intestinal bacteria involved in the etiology of rheumatoid arthritis? AMPIS, 100(1):1-9 (1992). The fact that there is a connection between bowel-related joint inflammation and bacteria give support to this hypothesis.  Tests with cell wall fragments from intestinal bacteria were found to produce joint inflammation in animal models.  Given that the human intestinal tract contains large amounts of these bacteria, it is reasonable to deduce that bacterial cell wall fragments may play a role in human arthritis of unknown etiology.

PubMed Reference    PMID:1536716

Hilpert H, Brussow H, Mietens C, Sidoti J, Lerner L, Werchau H. Use of bovine milk concentrate containing antibody to rotavirus to treat rotavirus gastroenteritis in infants. Journal of Infectious Diseases 156(1):158-166 . Infants hospitalized with rotavirus gastroenteritis that were given IgG from hyperimmunized cows showed a significant reduction in the duration of excretion of the virus compared to controls.

PubMed Reference    PMID:3110303

Huppertz H, Rutkowski S, Busch D, Eisebit R, Lissner R, Karch H. (1999) Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin producing E. coli, and E-coli expressing intimin and hemolysin. Journal of Pediatric Gastroenterology and Nutrition. 29(4):452-456 (1987). Pooled colostrum was given to infants infected with diarrheagenic E. coli, shiga toxin producing E. coli, or enterohemorrhagic E.coli expressing intimin and hemolysin experienced diminished frequency of loose stools compared to placebo.  The colostrum was well tolerated.

PubMed Reference    PMID:10512407

Jochims K, Kaup FJ, Drommer W, Pickel M. An immunoelectron microscopic investigation of colostral IgG absorption across the intestine of newborn calves. Research in Veterinary Science 57(1):75-80 (1994). Colostral IgG is transported across the intestinal boundary in newborn calves by specialized vesicles, called coated vesicles.

PubMed Reference    PMID:7973097

Keller MA, Heiner DC, Myers AS, Reisinger DM.  IgD in human colostrum.  Pediatric Research 19(1):122-126 (1985).  Concentrations of IgD in human colostrum were measured in a range from 2.2-410 µg/dl (mean concentration 35 µg/dl).

PubMed Reference    PMID:3969303

Kelleher SL. Lonnerdal B. Immunological activities associated with milk. Advances in Nutritional Research 10:39-65 (2001). Milk and colostrum not only provide the necessary nutritional requirements of the newborn but also establish the normal gut flora that inhibit the growth of pathogens and transfer maternal immunity to the infant.

PubMed Reference    PMID:11795053

Kelly CP, Pothoulakis C, Vavva F, Castagliuolo I, Bostwick EF, O'Keane JC, Keates S, LaMont JT. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotixicity of C. difficile toxins. Antimicrobial Agents and Chemotherapy 40(2):373-379 (1996). Immunoglobulin from hyperimmunized cows neutralizes the toxins from C. difficile, thus making it useful in prevention and treatment of C.difficile diarrhea.

PubMed Reference    PMID:8834883

Khazenson L, Gennad'eva T, Roshchin V, Krasheniuk A, Semenova N. Activity of bovine colostral IgG in the human digestive tract. Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii 9:101-106 (1980). The biological activity of bovine IgG from colostrum from cows hyperimmunized against Shigella sonnei was measured as it passed through the intestinal tracts of adults.  Although the concentration of intact IgG decreased as it passed through the tract, anti-Shigella activity remained high, indicating that the digestion of the intact IgG produced biologically active fragments.

PubMed Reference    PMID:7004026

Kohl S, Malloy, M, Pickering L, Morriss F, Adcock E, Walters D. Human colostral cytotoxicity: I. Antibody-dependent cellular cytotoxicity against herpes simplex viral-infected cells mediated by colostral cells. Journal of Clinical Laboratory Immunology. 1(3):221-224 (1978). Cells from colostrum in combination with antibody were able to kell Herpes simplex virus-infected cells.  Cells without the antibody had very low cytotoxicity.

PubMed Reference    PMID:756470

Korhonen H, Suvaoja EL, Ahola-Luttilia H, Sivela S, Kopola S, Husu J, Kosunen TU. Bactericidal effect of bovine normal and immune serum, colostrum and milk against Helicobactor pylori. Journal of Applied Bacteriology 78(6):655-662 (1995). Both serum and colostrum but not milk from cows was found to be highly bactericidal against H. pylori.

PubMed Reference    PMID:7615421

Korhonen H, Marnila P, Gill HS.  Milk immunoglobulins and complement factors.  British Journal of Nutrition 84(Suppl 1):S75-S80 (2000).  In bovine colostrum IgG1 accounts of 75% of the total Ig, followed by IgM, IgA and IgG2.

PubMed Reference    PMID:11242450

Kussendrager KD, van Hooijdonk AC.  Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications.  British Journal of Nutrition 84(Suppl 1):S19-S25 (2000).  Lactoperoxidase catalyzes the inactivation of a wide range of microorganisms by means of the lactoperoxidase system.

PubMed Reference    PMID:11242442

Lawton JW, Shortridge KF, Wong RL, Ng MH.  Interferon synthesis by human colostral leucocytes.  Archives of Diseases of Children 54(2):127-130 (1979).  Colostral leucocytes (white blood cells) stimulated to produce interferon did so, but were less efficient than blood leucocytes.

PubMed Reference    PMID:434888

LeFranc-Millot C, Vercaigne-Marko D, Wal J.-M, Lepretre A, Peltre G, Dhulster P, Guillochon D. Comparison of the IgE titers to bovine colostral G immunoglobulins and the F(ab')2 fragments in sera of patients allergic to milk. International Archives of Allergy and Immunology 110(2):156-162 (1996). IgE titers against colostral IgG were significantly higher in 36% of those suffering from milk allergy, while the digested fragments of IgG showed significantly less immunoreactivity while maintaining immunoreactivity.

PubMed Reference    PMID:8645993

Lehrer RI, Lichtenstein AK Ganz, T.  Defensins: antimicrobial and cytotoxic peptides of mammalian cells.  Annual Reviews of Immunology 11:105-128 (1993).  Defensins, small peptides containing 29-35 amino acids, are antimicrobial and cytotoxic components of the innate immune system.  They are known to be antimicrobial against both gram positive and gram negative bacteria, mycobacteria (tuberculosis and leprosy), Treponema pallidum (the spirochete that causes syphilis), many fungi, and some enveloped viruses.  They are also cytotoxic against a wide range of normal and malignant cells, including cells resistant to TNF-alpha and NK-cytolytic factor.    They act by attaching to the cell membranes of target microorganisms and cells, penetrating them and making them permeable, which leads to lysis.  Some defensins function as opsonins, some inhibit protein kinase C, some bind specifically to the ACTH receptor and block steroidogenesis, and some act as specific chemoattractants for monocytes.

Pubmed Reference    PMID:8476558

Lissner R, Thurmann P, Merz G, Karch, H. Antibody reactivity and fecal recovery of bovine immunoglobulins following oral administration of a colostrum concentrate from cows to healthy volunteers. International Journal of Clinical Pharmacology and Therapeutics 36(5):239-245 (1998). Pooled colostrum exhibited reactivity against proteins from Yersinia enterocolitica and Campylobacter jejuni, both powerful pathogens which cause gastrointestinal diseases.

PubMed Reference    PMID:9629986

Loimaranta V, Carlen A, Olsson J, Tenovuo J, Syvaoja E.-L, Korhonen H. Concentrated bovine colostral whey proteins from Streptococcus mutans/Strep. sobrinus immunized cows inhibit the adherence of Strep. mutans and promote the aggregation of mutans streptococci. Journal of Dairy Research 65(4):599-607 (1998). Colostral whey proteins from cows immunized against Streptococcus mutans and Streptococcus sobrinus were tested to determine their effect on adherence and aggregation of these two bacteria which cause dental cavities.  The whey from cows immunized against the bacteria significantly inhibited adherence and increased aggregation compared to whey from non-immunized cows.

PubMed Reference    PMID:9839215

Mach JP, Pahud JJ, Isliker H.  IgA with “secretory piece” in bovine colostrum and saliva.  Nature 223(209):952-955 (1969).  Secretory IgA found in bovine colostrum.

PubMed Reference    PMID:4184794

Michalek SM, McGhee JR. Effective immunity to dental caries: passive transfer to rats to antibodies to Streptococcus mutans elicits protection. Infection and Immunity 17(3):644-650 (1977). IgG derived from colostrum, milk and blood serum of rats immunized against Streptococcus mutans (which cause dental cavities) effectively immunized the offspring of these rats against the bacteria.  Fewer cavities were found in the offspring than in non-immunized rats.
PubMed Reference    PMID:903178

Mickelson KN, Moriarty KM.  Immunoglobulin levels in human colostrum and milk.  Journal of Pediatric Gastroenterology and Nutrition 1(3):381-4 (1982).  Levels of sIgA, IgG and IgM were determined in human colostrum and milk.  A mean concentration of 32 g/L was found for sIgA (1.5-83.7 g/L), 1.13 g/L for IgM and 0.53 g/L for IgG.  While total amounts declined with time postpartum, relative proportions remained the same.

PubMed Reference    PMID:7186050

Milgrom H.   Attainments in atopy: special aspects of allergy and IgE.  Advances in Pediatrics 49:273-297 (2002). Allergy is characterized by elevated levels of specific IgE in the blood, called “atopy”.  Therapy with anti-IgE has shown promise in inhibiting early- and late-phase allergic reactions and asthma.  [Colostrum contains both IgE and IgE-blockers.]

PubMed Reference    PMID:12214775

Mitra AK, Mahalanabis D, Ashraf H, Unicomb L, Eeckels R, Tzipori S. Hyperimmune cow colostrum reduces diarrhoea due to rotavirus: a double-blind, controlled clinical trial. Acta Paediatrica 84(9):996-1001 (1995). Colostrum from cows immunized against four strains of rotavirus (the leading cause of diarrhea in infants) was given to infants aged 6-24 months who were infected with the virus.  Those receiving the colostrum experienced a 29% reduction in the duration of the diarrhea compared to the control group, and diarrhea stopped in 50% of them whereas all of the control group continued to experience diarrhea.

PubMed Reference    PMID:8652974

Mohan P, Haque K. Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants. Cochrane Database System Review 3:CD003740 (2003). Rotavirus is the most common neonatal virus infection, causing severe diarrhea, and is potentially lethal to low birth weight infants.  Boosting mucosal immunity with orally administered immunoglobulin from colostrum can help prevent infection.  No adverse effects have been reported in trials.

PubMed Reference    PMID:12917985

Nord J, Ma P, DiJohn D, Tzipori S, Tacket CO. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS. 4(6):581-584 (1990). Cryptosporidium parvum can cause severe, debilitating diarrhea in AIDS patients. In this pilot study, treatment with hyperimmune colostrum against C. parvum showed promise in treating patients with cryptosporidosis.

PubMed Reference    PMID:2201320

Ogra P, Losonsky G, Fishaut M. Colostrum-derived immunity and maternal-neonatal interaction. Annals of the New York Academy of Sciences 409:82-95 (1983). Colostrum from the mother is important in establishing the immune system in newborn humans.

PubMed Reference    PMID:6347005

Ogra SS, Ogra PL. Immunologic aspects of human colostrum and milk. I. Distribution characteristics and concentrations of immunoglobulins at different times after the onset of lactation. Journal of Pediatrics. 92(4):546-549 (1978). While levels of IgG remain fairly constant following the onset of lactation, levels if IgA and IgM decline rapidly in humans.

PubMed Reference    PMID:416193

Ouwehand A, Salminen S, Skurnik M, Conway P. Inhibition of pathogen adhesion by B-lactoglobulin. International Dairy Journal. 7:685-692 (1997). Beta-lactoglobulin, a component of colostrum, inhibited the adhesion of Klebsiella oxytoca and a strain of fimbriae-expressing E. coli to immobilized iliostomy glycoproteins (a model of intestinal mucosa).  Inhibition of adhesion may prevent colonization of pathogens at an early stage of infection.

Palmer EL, Gary Jr. GW, Black R, Martin ML. Antiviral activity of colostrum and serum immunoglobulins A and G. Journal of Medical Virology. 5(2):123-129 (1980). Human colostrum contains IgA specific to enteric virus but no virus-specific IgG.
PubMed Reference    PMID:6246196

Parodi PW. Cows' milk fat components as potential anticarcinogenic agents. Journal of Nutrition 127(6):1055-1060 (1997). Conjugated linoleic acid, a component of cow's milk and colostrum, inhibits proliferation of human malignant melanoma, colorectal, breast and lung cancer cell lines. It also has been shown to reduce the incidence of chemically induced mouse epidermal tumors, mouse forestomach neoplasia, and aberrant crypt foci in rats.  It also inhibits mammary tumorogensis. Sphingomyelin, one of the phospholipids in colostrum and milk, participates in three major antiproliferative pathways - inhibition of cell growth, induction of differentiation, and apoptosis (programmed cell death) - through its biologically active metabolites ceramide and sphingosine. Milk triaglycerides also contain butyric acid, a potent inhibitor of proliferation and inducer of differentiation and apoptosis in a wide range of neoplastic cell lines. Other anti-cancer components of colostrum and milk include beta-carotene, beta-ionone and gossypol.

PubMed Reference    PMID:9187617

Paulik S, Slanina L, Polacek M.  [Lysozyme in the colostrum and blood of calves and dairy cows]  Veterinarni Medicina 30(1):21-28 (1985).  In first colostrum the lysozyme concentration fluctuated within the range of 0.15 to 0.65 µg/ml, with an average of 0.30 µg/ml. The concentration of lysozyme and immunoglobulins of the IgG and IgM class in colostrum showed a contrary trend in first and second milk yield, with a tendency towards increase for lysozyme and towards decrease for immunoglobulins.

PubMed Reference    PMID:3918380

Petschow B, Talbott R. Reduction in virus-neutralizing activity of a bovine colostrum immunoglobulin concentrate by gastic acid and digestive enzymes. Journal of Pediatric Gastroenterology and Nutrition . 19(2):228-235 (1994). Gastric acid and pancreatic trypsin (a digestive enzyme) reduce the biological activity of bovine milk antibodies as they pass through the digestive tract.

PubMed Reference    PMID:7815246

Petzoldt K, von Benten C. Passive allergisation of calves and lambs due to colostral antibodies. Annales de recherches vétérinaires 9(2):235-238 (1978). This study demonstrates that newborn calves are passively sensitized by oral intake of maternal anaphylactic antibodies.

PubMed Reference    PMID:747320

Pincus C, Nussenweig V. Regulation of the Immune Response: Suppressive and enhancing effects of passively administered antibody. Journal of Experimental Medicine. 133(5):987-1003 (1971). The immune response can be modulated through the passive administration of antibody, such as the IgG in colostrum.

PubMed Reference    PMID:4101806

Plettenberg A, Stoehr.A, Stellbrink J, Albrecht H, Meigel W. A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. Clinical Investigator 71(1):42-45 (1993). Treatment with 10 grams of IgG from bovine colostrum per day led to either partial or complete remission of symptoms in 64% of tested patients with chronic refactory diarrhea due to HIV infection.

PubMed Reference    PMID:8453259

Quigley JD, Martin KR, Dowlen HH, Wallis LB, Lamar K. Immunoglobulin concentration, specific gravity, and nitrogen fractions of colostrum from Jersey cattle. Journal of Dairy Science 77(1):264-269 (1994). Colostrum collected from cows as soon after parturition as possible and analyzed for levels of immunoglobulin, fat and nitrogen. IgG content decreased and IgA content increased with time in the colostrum.

PubMed Reference    PMID:8120194

Radosevich JK, Scott GH, Olson GB. Delayed-type hypersensitivity responses induced by bovine colostral components. American Journal of Veterinary Research, 46(4):875-878 (1985).  Transfer factor-type substances obtained from leukocytic cells and fluid portions of bovine colostrum caused effective passive transfer of delayed-type hypersensitivity responses across species barriers. Passive transfer of Brucella abortus sensitivity was obtained when using components derived from colostrum of dams sensitized at 3 and 9 months of age. Colostral feedings to calves caused the passive transfer of delayed-type hypersensitivity as early as 2 days after parturition. The findings indicated that colostral components were important in the process of cell-mediated immunity.

PubMed Reference    PMID:3925823

Rudloff HE, Schmalstieg FC Jr, Mushtaha AA, Palkowetz KH, Liu SK, Goldman AS.  Tumor necrosis factor-alpha in human milk.  Pediatric Research 31(1):29-33 (1992).  Tumor necrosis factor-alpha is found in human colostrum and milk in sufficient quantities to affect the immune system of the infant.

PubMed Reference    PMID:1375729

Rudloff HE, Schmalstieg FC Jr, Palkowetz KH, Paszkiewicz EJ, Goldman AS.  Interleukin-6 in human milk.  Journal of Reproductive Immunology 23(1):13-20 (1993).  IL-6 was found in human milk (colostrum) collected during the first two days of lactation using radioimmunoassay and column chromatography.

PubMed Reference    PMID:8429522

Rump JA, Arndt R, Arnold A, Bendick C, Dichtelmuller H, Franke M, Helm EB, Jager H, Kampmann B, Kolb P. Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Clinical Investigator. 70(7):588-594 (1992). Diarrhea and weight loss are seen in over 50% of AIDS patients.  In severe cases, symptoms can be very severe, leading to death even in the absence of opportunistic infections. Use of immunoglobulins from colostrum resulted good therapeutic effects in 19 HIV immunodeficient patients with chronic diarrhea, 2 patients with common variable immunodeficiency, one unidentified immunodeficiency, and 5 with graft-vs-host disease following bone marrow transplant.

PubMed Reference    PMID:1392428

Sabin, AB. Antipoliomyelitic substance in milk from human beings and certain cows.  Journal of Diseases of Children, 80(5):866-867 (1950).  Dr. Albert Sabin used antibodies from colostrum in designing his first oral polio vaccine.

PubMed Reference    PMID:14777169

Sabin AB, Fieldsteel AH. Antipoliomyelitic activity of human and bovine colostrum and milk.  Pediatrics 29(1):105-115 (1962).

PubMed Reference    PMID:14495782

Saif L, Smith K. Enteric viral infections of calves and passive immunity. Journal of Dairy Science. 68(1):206-228 (1985). Coronavirus and rotavirus both cause diarrhea in newborn calves. IgG1 antibodies in colostrum from immunized cows helps prevent diarrhea and viral shedding in calves.

PubMed Reference    PMID:2984270

Sandholm M, Honkanen-Buzalski T. Colostral trypsin-inhibitor capacity in different animal species. Acta Veterinaria Scandinavica 20(4):469-476 (1979). Colostrum contains a trypsin (digestive enzyme) inhibitor that helps protect IgG and other components of colostrum from digestion in the gastrointestinal tract.

PubMed Reference    PMID:546206

Sarker SA, Casswall TH, Mahalanabis D, Alam NH, Albert MJ, Brussow H, Fuchs GJ, Hammerstrom L. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatric Journal of Infectious Disease 17(12):1149-1154 (1998). Children suffering from rotavirus diarrhea were successfully treated with anti-rotavirus IgG from bovine colostrum.

PubMed Reference    PMID:9877365

Service, R. Triggering the First Line of Defense. Science 265(5178):1522-1524 (1994). A review article highlighting the importance of oral immunoglobulin supplementation and other synthetic compounds in activating mucosal immunity.

PubMed Reference    PMID:8079164

Seto A, Okabe T, Ito Y. Immunoglobulin M associated with secretory component and immunoglobulin A deficiency in bovine colostrum.  American Journal of Veterinary Research 38(11):1895-1896 (1977).  IgM was found in bovine colostrum associated with the secretory component of sIgA.

PubMed Reference    PMID:73358

Shi M, Hao S, Chan T, Xiang J. CD4+ T cells stimulate memory CD8+ T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion.  Journal of Leukocyte Biology 80(6): 1354-1363 (2006).  CD8+ memory T cell expansion following a second encounter with a pathogen is a hallmark of adaptive immunity.  Antigen-specific CD4+ cells, activated by dendritic cells, stimulate the this expansion of CD8+ cells.

PubMed Reference    PMID:16980510

Shortridge K, Lawton J, Choi E. Protective potential of colostrum and early milk against prospective influenza viruses. Journal of Tropical Pediatrics. 36(2):94-95 (1990). Colostrum can also protect against influenza viruses.

PubMed Reference    PMID:2355411

Siber G. Immune globulin to prevent nosocomial infection. New England Journal of Medicine. 327(4):269-271 (1992). IgG from colostrum can help prevent nosocomial infections, i.e. infections which are a result of treatment in a hospital.

PubMed Reference    PMID:1614468

Stephen W, Dichtelmuller H, Lissner R. Antibodies from colostrum in oral immunotherapy. Journal of Chemical Clinical Biochemistry 28(1):19-23 (1990). An IgG preparation made from colostrum proved highly effective in the treatment of severe diarrhea, such as in AIDS patients. It had high levels of antibacterial antibody and a high capacity for bacterial toxin neutralization.

PubMed Reference    PMID:2313232

Stelwagen K, Carpenter E, Haigh B, Hodgkinson A, Wheeler TT.  Immune Components of Bovine Colostrum and Milk.  Journal of Animal Science epub ahead of print (2008).  Human and bovine colostrum contain cytokines and antimicrobial proteins and peptides, including lactoferrin, defensins and cathelicidins.

PubMed Reference    PMID:18952725

Swarbrick ET, Stokes CR, Soothill JF. Absorption of antigens after oral immunisation and the simultaneous induction of specific systemic tolerance. Gut 20(2):121-125 (1979). Antigens (foreign proteins, pathogenic microbes) can be absorbed through the intestinal lining intact. Feeding of an antigen may reduce the subsequent absorption of that antigen, which is a function of local immunity in the gut.  It can also contribute to tolerance of the antigen, which is important in allergies.

PubMed Reference    PMID:428823

Swarbrick ET. The Handling of Ingested Antigens. In: The Immunology of Infant Feeding, Plenum Press, NY, Wilkinson AW, ed., pp. 13-20 (1981).  During the first 24-36 hours after birth, a newborn's bowel wall has a large number of open pores through which large the immunoactive molecules found in colostrum can enter the body.

Tacket CO, Binion SB, Bostwick E, Losonsky G, Roy MJ, Edelman R. Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. American Journal of Tropical Medicine and Hygiene 47(3):276-283 (1992). Orally administered bovine IgG concentrate protects against shigellosis and may be useful in preventing shigellosis ("traveler's diarrhea" ) in travelers, military personnel and other people at risk.

PubMed Reference    PMID:1524140

Takahashi T, Nakagawa E, Nara T, Yajima T, KuwataT. Effects of Orally Ingested Bifidobacterium longum on the Mucosal IgA response of Mice to Dietary Antigens. Bioscience, Biotechnology and Biochemistry 62(1):10-15 (1998). Mice were fed whey protein with and without Bifidobacterium longum cultures.  Then they were fed beta-lactoglobulin, a common cause of milk allergy.  Those fed the whey with bacteria cultures had higher total IgA and anti-beta-lactoglobulin IgA levels than the control group. This suggests that lactic acid bacteria help protect the host from bacterial invasion of the intestinal mucosa.

PubMed Reference    PMID:9501512

Takahata Y, Takada H, Nomura A, Ohshima K, Nakayama H, Tsuda T, Nakano H, Hara T.  Interleukin-18 in human milk.  Pediatric Research 50(2):268-272 (2001).  Human colostrum contains significantly more IL-18 than transitional and mature milk.

PubMed Reference    PMID:11477214

Takahata Y, Takada H, Nomura A, Nakayama H, Ohshima K, Hara T.  Detection of interferon-gamma-inducible chemokines in human milk.  Acta Paediatrica 92(6):659-665 (2003).  Two chemokines in human colostrum and milk, IP-10 and MIG, both inducible by interferon gamma, may contribute to the migration and activation of intestinal T lymphocytes to enhance mucosal immunity during the early neonatal period.

PubMed Reference    PMID:12856973

Thatcher EF, Gershwin LJ.  Colostral transfer of bovine immunoglobulin E and dynamics of serum IgE in calves.  Veterinary Immunology and Immunopathology 20(4):325-334 (1989).  Blood serum levels of IgE in calves was high for the first week postpartum, after which levels declined until 12 weeks of age, when they began to increase again.  This suggests that passive transfer of IgE from the mother via colostrum is important in providing the calf immune protection during the first weeks of life.

PubMed Reference    PMID:2718373

Thomas EL, Pera KA, Smith KW, Chwang AK.  Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobial system.  Infection and Immunity 39(2):767-778 (1983). The lactoperoxidase system inhibits the growth of Streptococcus mutans in culture dependent on pH, amount of hydrogen peroxide present, cell sulfhydryl content and stored carbohydrate content.

PubMed Reference    PMID: 6832819

Tyrell D. Breastfeeding and viral infections. In: The Immunology of Infant Feeding, Plenum Press, NY, Wilkinson AW, ed., pp. 55-62, 1981. Breast fed babies are much less likely to experience bronchiolitis due to RSV (respiratory syncitial virus) than bottle fe babies. The antiviral activity of mil and colostrum is partially due to antibodies (immunoglobulins) and partially due to other causes, possibly polysaccharides found on a number of the constituents of colostrum. The main effect of these components of colostrum and milk take place in the gut.

Tzipori S, Roberton D, Chapman C. Remission of diarrhoea due to cryptosporidiosis in an immunodeficient child treated with hyperimmune bovine colostrum. British Medical Journal 293(6557):1276-1277 (1986). A young boy suffering from poor weight gain, diarrhea, Pneumocystis carinii infection, and hypogammaglobulinaemia (insufficient gamma globulin production) developed cryptosporidosis. Treatment with hyperimmune bovine colostrum resolved the diarrhea and vomiting within 5 days and oocysts were no longer seen after 8 days.

PubMed Reference      PMID:3096462

Ulcova-Gallova Z, Fialova P, Krauz V. (1994) Immunologic factors in human colostrum and milk. Casopis Lekaru Ceskych 133(9):275-6. The mammary can be conceived of as an immunological secretory organ producing both specific and non-specific immunological factors that are transmitted in both colostrum and milk.

PubMed Reference     PMID:8194096

Ungar BLP, Ward DJ, Fayer R, Quinn CA. Cessation of Cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum. Gastroenterology 98(2):486-489 (1990). Hyperimmune bovine colostrum successfully treated an HIV patient with Cryptosporidium-associated diarrhea of three months duration. The patient remained asymptomatic for 3 months after treatment.

PubMed Reference     PMID:2295405

Ushijima H, Dairaku M, Honnma H, Mukoyama A, Kitamura T. Immunoglobulin components and anti-viral activities in bovine colostrum. Kansenshogaku Zasshi 64(3):274-279 (1990). IgG, IgM and IgA were found in bovine colostrum with neutralization activity against bovine, simian and human rotaviruses.

PubMed Reference     PMID:2162896

van Hooijdonk AC, Kussendrager KD, Steijns JM.  In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defense.  British Journal of Nutrition  84(Suppl 1):S127-34 (2000).  Of the antimicrobial and antiviral components of bovine milk and colostrum, lactoferrin and lactoperoxidase that appear to be very promising for use in fish farming, animal husbandry, oral hygiene and functional foods.  Other components, particularly lipids and antimicrobial peptides, such as PRP, also show promise.

PubMed Reference    PMID:11242457

Veselsky L, Cechova D, Jonakova V. Secretion and Immunochemical Properties of the Trypsin Inhibitor from Bovine Colostrum. Hoppe-Seyler's Zeitschrift für Physiolgische Chemie 359(8):873-878 (1978). A trypsin inhibitor was found in bovine colostrum.  Antisera to the inhibitor showed reactivity against a trypsin inhibitor from pig colostrum as well.

PubMed Reference    PMID:361534

Waldman RH, Stone J, Lazzell V, Bergmann KC, Khakoo R, Jacknowitz A, Howard S, Rose C. (1983) Oral route as method for immunizing against mucosal pathogens. Annals of the New York Academy of Science 409:510-6. Oral immunization, such as with colostral IgG, may prove to be far superior than shots in protecting against pathogens which attack the mucosal linings of the body.

PubMed Reference     PMID:6346997

Walker M. Bovine colostrum offers broad-spectrum benefits for wide-ranging ailments. Townsend Letters for Doctors and Patients. 74-80 (1999).

Walker M. Infectious bugs are back but there's a remedy. Townsend Letters for Doctors and Patients (1995).

Wijkstrom-Frei C, El Chemaly S, Ali-Rachedi R, Gerson C, Cobas MA, Forteza R, Salathe M, Conner GE.  Lactoperoxidase and Human Airway Host Defense.  American Journal of Respiratory Cell and Molecular Biology 29(2):206-212 (2003).  A functional lactoperoxidase system exists in human airways and may contribute to host defense against infection.

PubMed Reference    PMID:12626341

Yamada M, Murakami K, Wallingford JC, Yuki Y.  Identification of low-abundance proteins of bovine colostral and mature milk using two-dimensional electrophoresis followed by microsequencing and mass spectrometry.  Electrophoresis 23(7-8):1153-1160 (2002).  After removing two of the most abundant proteins in bovine colostrum, IgG and beta-casein, a number of enzymes and other proteins were found in small amounts, including alpha-lactalbumin, beta-lactoglobulin, fibrinogen beta-chain, chitinase 3-like 1, alpha-antitrypsin, complement C3 alpha chain, gelsolin, and apolipoprotein H.  Their presence may have physiologic relevance to the health and development of the newborn.

PubMed Reference    PMID:11981865

Ylitalo S, Uhari M, Rasi S, Pudas J, Leppaluoto J. Rotaviral antibodies in the treatment of acute rotaviral gastroenteritis. Acta Paediatrica 87(3):264-267 (1998). Hyperimmune bovine colostrum showed some improvement in the duration and severity of rotaviral diarrhea in otherwise healthy, well-fed children, but the results were not statistically significant.

PubMed Reference    PMID:9560031

Yolken RH. Losonsky GA, Vonderfecht S, Leister F, Wee SB. Antibody to human rotavirus in cow's milk. New England Journal of Medicine 312(10):605-610 (1985). Antibodies against human rotavirus were found in both raw and unpasteurized milk but not infant formula.

PubMed Reference    PMID:2983202

Yoshioka, Y, Kudo, S, Nishimura, H, Yajima, T, Kishihara, K, Saito, K, Suzuki, T, Suzuki, Y, Kuroiwa, S, Yoshikai, Y. Oral administration of bovine colostrum stimulates intestinal intraepithelial lymphocytes to polarize Th1-type in mice.  International Immunopharmacology 5(3):581-590 (2005).  Stimulating the Th1 immune response  from the Th2 skewed immune response in infancy is important to reduce the incidence of allergies.  Mice given colostrum showed a polarization to Th1 response in intestinal intraepithelial lymphocytes while intestinal microflora and IgA levels showed no change.  This suggests that colostrum may protect from both infectious disease and allergies mediated by Th2 type responses.

PubMed Reference    PMID:15683853

Yu VY. Scientific rationale and benefits of nucleotide supplementation of infant formula. Journal of Paediatrics and Child Health 38:543–549 (2002).  Nucleotides, present in colostrum and milk, may enhance the immunity of the newborn.  Nucleotides are believed to play an immunomodulatory role.

PubMed Reference    PMID:12410863

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