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 investigate their effects on cytokine (TNF-α and IL-6) production and nitric oxide (NO) release by murine bone marrow macrophages (BMMs). The results showed that these peptides alone were incapable of stimulating cytokine production or NO release in naive or IFN-γ-primed BMMs. However, when BMMs were co-incubated with the peptides at a concentration of 1.0 µM and lipopolysaccharide (LPS; 100 ng ml−1), an augmentative effect on TNF-α, IL-6 and NO production was observed. Of the three peptides, TTMPLW had the greatest augmentative effect on NO production by LPS-stimulated BMMs and induced the highest amount of TNF-α production at a concentration of 1.0 µM. All the peptides at a concentration of 1.0 µM stimulated IL-6 production by BMMs. TNF-α was neutralised by anti-TNF-α monoclonal antibody and the release of NO was reduced by about 33.3% (p < 0.01). These results demonstrate that bovine casein peptides can co-stimulate naive macrophages with LPS for proinflammatory cytokine production and NO release and may play a role in host defence against pathogens. © 2000 Society of Chemical Industry