In vitro regulation by muramyl dipeptide of interferon production from peripheral blood mononuclear cells of healthy volunteers

We investigated the effect of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) on interferon (IFN)-alpha and -gamma production by peripheral blood mononuclear cells from healthy subjects. MDP, on its own, was found to lack the ability to induce IFN production. However, this synthetic adjuvant was able to modulate IFN production induced by other stimuli. In cultures from a considerable number of tested donors, MDP enhanced IFN-gamma levels induced by phytohaemagglutinin. This effect was further potentiated after depleting the PBMNC cultures of their adherent cells. In contrast, MDP significantly suppressed the Sendai virus-induced IFN-alpha and this effect was reversed following adherent cell depletion. Identical regulatory effects on IFN production were exerted by the adjuvant active analogue of MDP, namely murabutide. The adjuvant inactive stereoisomer, MDP (DD) exhibited a similar enhancing effect on IFN-gamma but had a significantly lower inhibitory activity on IFN-alpha production. The potential value of this generation of immunomodulators in the treatment of viral infections and in models for studying the regulation of IFN at the molecular level is discussed.