Bovine casein peptides co-stimulate naive macrophages with lipopolysaccharide for proinflammatory cytokine production and nitric oxide release

Three bovine casein peptides, ie LLY, PGPIPN and TTMPLW, were used to inves tigate their effects on cytokine (TNF-alpha and IL-6) production and nitric oxide (NO) release by murine bone marrow macrophages (BMMs). The results s howed that these peptides alone were incapable of stimulating cytokine prod uction or NO release in naive or IFN-gamma -primed BMMs. However, when BMMs were coincubated with the peptides at a concentration of 1.0 muM and Lipop olysaccharide (LPS; 100ng ml(-1)), an augmentative effect on TNF-alpha, IL- 6, and NO production was observed. Of the three peptides, TTMPLW had the gr eatest augmentative effect on NO production by LPS-stimulated BMMs and indu ced the highest amount of TNF-alpha production at a concentration of 1.0 mu M. All the peptides at a concentration of 1.0 muM stimulated IL-6 productio n by BMMs. TNF-alpha was neutralised by anti-TNF-alpha monoclonal antibody and the release of NO was reduced by about 33.3% (p <0.01). These results d emonstrate that bovine casein peptides can co-stimulate naive macrophages w ith LPS for proinflammatory cytokine production and NO release and may play a role in host defence against pathogens. (C) 2000 Society of Chemical Ind ustry.