INTERFERON-GAMMA TUMOUR NECROSIS FACTOR-ALPHA SYNERGISM AS A MECHANISM FOR ENHANCED NITRIC-OXIDE PRODUCTION FOLLOWING IN-VIVO ADMINISTRATION OF MURAMYL DIPEPTIDE (MDP) TO MICE/

The aim of the present study was to investigate the role of muramyl di peptide (MDP) in triggering host non-specific defence mechanisms, name ly its influence upon the L-arginine-dependent biotransformation pathw ays leading to formation of nitric oxide (NO). MDP was applied subcuta neously to mice as one or three dairy injections, 300 mu g MDP each. P roduction of NO by peritoneal macrophages from these animals or the ca pability of their splenocytes to render virgin macrophages for enhance d NO production was assayed. It has been found that macrophages from M DP-treated animals produce considerably enhanced amounts of NO and tha t the splenocytes secrete soluble factors providing all the signals re quired for induction of NO biosynthesis. Introduction of anti-IFN-gamm a or anti-TNF-alpha antibodies into these splenocyte supernatants resu lted in complete suppression of inducible NO production by macrophages .