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Immunoregulatory peptides in bovine milk

  • Harsharnjit S. Gill (a1), F. Doull (a1), K. J. Rutherfurd (a1) and M. L. Cross (a1)

Bovine milk is known to contain a number of peptide fractions that can affect immune function. The vast majority of immunoregulatory peptides that have been characterised are hydrolysate derivatives of major milk proteins. Recent research has also indicated that the metabolic activity of probiotic lactic acid bacteria can generate de novo immunoregulatory peptides from milk, via enzymatic degradation of parent milk protein molecules. In contrast, relatively little is known of endogenous, preformed immunoregulatory peptides in milk that may be relevant to modulating human health. The natural in vivo role of preformed and enzymatically derived peptides is likely to be one of regulation of the neonatal (bovine) gastrointestinal tract immune system, in order to modulate immune function with respect to the development of immunocompetence and avoidance of undesirable immunological responses (e.g. tolerance, and hypersensitivity to nutrients). There is scope for the further characterisation of both the origin and function of milk-derived immunoregulatory peptides, so that their potential to influence human health can be fully appraised. This review highlights our current knowledge of milk-derived immunoregulatory peptides, and outlines areas that are of relevance for further research.

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Corresponding author
*Corresponding author: Professor H. S. Gill, fax +64 6 350 5446, email
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Blach-Olszewska, Z, Janusz, M (1997) Stimulatory effect of ovine colostrinine (a proline-rich polypeptide) on interferons and tumor necrosis factor production by murine resident peritoneal cells Archivum Immunologiae et Therapiae Experimentalis 45, 4347.
Bounous, G, Kongshavn, PAL (1982) Influence of dietary proteins on the immune system of mice Journal of Nutrition 112, 17471755.
Bounous, G, Kongshavn, PAL (1985) Differential effect of dietary protein type on the B cell and T cell responses in mice Journal of Nutrition 115, 14031408.
Coste, M, Tome, D (1991) Milk peptides with physiological activities. II Opioid and immunostimulating peptides derived from milk proteins Lait 71, 241247.
Elitsur, Y, Luk, GD (1991) Beta-casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation Clinical and Experimental Immunology 85, 493497.
Elitsur, Y, Neace, C, Liu, X, Dosescu, J, Moshier, JA (1997) Vitamin A and retinoic acids immunomodulation on human gut lymphocytes Immunopharmacology 35, 247253.
Fiat, AM, Migliore-Samour, D, Jolles, P, Drouet, L, Sollier, CB, Caen, J (1993) Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities Journal of Dairy Science 76, 301310.
Guimont, C, Marchall, E, Girardet, JM, Linden, G (1997) Biologically active factors in bovine milk and dairy byproducts, Influence on cell culture Critical Reviews in Food Science and Nutrition 374, 393410.
Janusz, M, Wieczorek, Z, Spiegel, K, Kubik, A, Szewczuk, Z, Siemion, I, Lisowski, J (1987) Immunoregulatory properties of synthetic peptides, fragments of a proline-rich polypeptide (PRP) from ovine colostrum Molecular Immunology 24, 1029.
Jolles, P, Fiat, A-M, Migliore-Samour, D, Drouet, L, Caen, J, BRenner, and GSawatzki (1992) Peptides from milk proteins implicated in antithrombosis and immunomodulation New Perspectives in Infant Nutrition, Symposium Antwerp 160172.
Jolles, P &, Migliore-Samour, D (1986) Preparation of immunological agents by treating lipid-free bovine casein with proteolytic enzyme and fractionating the product. Patent Assignee: Rhone-Poulenc Sante. WPI Acc No, 86037423/06, United States Patent 4 851 509, European Patent 170 550.
Jolles, P, Migore-Samour, D &, Parker, F (1988) Immuno stimulant substances derived from bovine casein and compositions containing the same. Patent Assignee: Rhone-Poulenc Sante. United States Patent 4 777 243.
Julius, MH, Janusz, M, Lisowski, J (1988) A colostral protein that induces the growth and differentiation of resting B lymphocytes Journal of Immunology 140, 1366.
Kayser, H, Meisel, H (1996) Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins FEBS Letters 383, 1820.
Lahov, E, Regelson, W (1996) Antibacterial and immunostimulating casein-derived substances from milk, casecidin, isracidin peptides Food and Chemical Toxicology 34, 131145.
Maruyama, S, Mitacki, H, Awaya, J, Kurono, M, Tomizuka, N, Suzuki, H (1987) Angiotensin I-converting enzyme inhibitory activity of the C-terminal hexapeptide of alpha S1 casein Agricultural and Biological Chemistry 51, 25572561.
Mattsby-Baltzer, I, Roseanu, A, Motaas, C, Elverfors, J, Engberg, I, Hanson, LA (1996) Lactoferrin or a fragment thereof inhibits the endotoxin-induced interleukin-6 response in human monocytic cells Pediatric Research 40, 257262.
Meisel, H (1997) Biochemical properties of regulatory peptides derived from milk proteins Biopolymers 43, 119128.
Migliore-Samour, D, Jolles, P (1988) Casein, a prohormone with an immunomodulating role for the newborn? Experientia 44, 188193.
Miyauchi, H, Hashimoto, S, Nakajima, M, Shinoda, I, Fukuwatari, Y, Hayasawa, H (1998) Bovine lactoferrin stimulates the phagocytic activity of human neutrophils, identification of its active domain Cellular Immunology 187, 3437.
Otani, H, Hata, I (1995) Inhibition of proliferative responses of mouse spleen lymphocytes and rabbit Peyer's patch cells by bovine milk caseins and their digests Journal of Dairy Research 62, 339348.
Otani, H, Monnai, M, Kawasaki, Y, Kawakami, H, Tanimoto, M (1995) Inhibition of mitogen-induced proliferative responses of lymphocytes by bovine κ-caseinoglycopeptides having different carbohydrate chains Journal of Dairy Research 62, 349357.
Parker, F, Migliore-Samour, D, Floc'h, F (1984) Immunostimulating hexapeptide from human casein, amino acid sequence, synthesis and biological properties European Journal of Biochemistry 145, 677682.
Schanbacher, FL, Talhouk, RS, Murray, FA (1997) Biology and origin of bioactive peptides in milk Livestock Production Science 50, 105123.
Schlimme, E, Meisel, H (1995) Bioactive peptides derived from milk proteins. Structural, physiological and analytical aspects Die Nahrung 39, 120.
Shinoda, I, Takase, M, Fukuwatari, Y, Shimamura, S, Koller, M, Konig, W (1996) Effects of lactoferrin and lactoferricin on the release of interleukin 8 from human polymorphonuclear leucocytes Bioscience, Biotechnology and Biochemistry 60, 521523.
Stoeck, M, Ruegg, C, Miescher, S, Carrel, S, Cox, D, Fliedner, V, Alkan, S, VonFliedner, V (1989) Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta1 and beta2 Journal of Immunology 143, 32583265.
Sutas, Y, Hurme, M, Isolauri, E (1996) Down-regulation of anti-CD3 antibody-induced IL-4 production by bovine caseins hydrolysed with Lactobacillus GG-derived enzymes Scandinavian Journal of Immunology 43, 687689.
Sutas, Y, Soppi, E, Korhonen, H (1996) Suppression of lymphocyte proliferation in vitro by bovine caseins hydrolyzed with Lactobacillus casei GG-derived enzymes Journal of Allergy and Clinical Immunology 98, 216224.
Svedberg, J, DeHaas, J, Leimenstoll, G, Paul, F, Teschemacher, H (1985) Demonstration of β-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans Peptides 6, 825.
Werner, GH, Floc'h, F, Migliore-Samour, D, Jolles, P (1986) Immunomodulating peptides Experientia 42, 521531.
Yun, SS, Sugita-Konishi, Y, Kumagai, S, Yamauchi, K (1996) Isolation of mitogenic glycophosphopeptides from cheese whey protein concentrate Bioscience, Biotechnology and Biochemistry 60, 429433.
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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