Immunosuppresive action of milk k-casein and its digests

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The results obtained for 2 years (1996 and 1997) are summarized as follows :1. Bovine kappa-casein and it glycomacropeptide (residues 106-169, CGP) completely inhibited mouse T-lymphocyte proliferation via at least 2 different mechanisms : production of interleukin-1 receptor antagonist and suppression of interleukin-2 receptor expression on CD4+ T-lymphocytes.2. Reverse transcription-polymerase chain reaction analysis showed that macrophages transcribed interleukin-1 receptor antagonist mRNA in both the absence and the presence of CGP.CGP increased interleukin-1 receptor antagonist biosynthesis and/or secretion without influencing secretion level of interleukin-1 alpha and interleukin-1 beta.3. Bovine kappa-casein significantly inhibited macrophage activation and phagocytosis of macrophages. Both inhibitory activities was little influenced by trypsin or chymotrypsin digestion while pepsin digestion changed the inhibitory activity into an enhancing activity.4. Orally ingestion of bovine CGP suppressed the level of serum IgG antibodies specific to dietary protein and intraperitoneally injected protein in mice. Mitogenic responses of spleen cells indicated that the suppressor T-lymphocyte number and/or function were significantly increased in mice fed the CGP-added diet.5. Human CGP revealed a cytotoxic activity when the peptide was incubated with mouse lymphocytes. In addition, the chromatin of lymphocytes incubated with human CGP coagulated and DNAs extracted from the cells segmented. These results suggested that human CGP had an apoptosis-inducing ability.Cytotoxic activity was also produced when bovine CGP was digested with trypsin.These results suggest that kappa-casein and its digest may contribute to anti-inflammatory response in neonatal intestine. In addition, CGP prepared from cheese whey is available as an ingredient to prepare immunosuppressive foods