IN-VITRO TNF-ALPHA PRODUCTION AND IN-VIVO ALTERATION OF TNF-ALPHA RNAIN MOUSE PERITONEAL-MACROPHAGES AFTER TREATMENT WITH DIFFERENT BACTERIAL DERIVED AGENTS

Since muramyl dipeptide (MDP) was recognized as a potent monocyte/macr ophage activating agent, many MDP analogues were synthesized and teste d for their ability to augment the host immune defence system against neoplasms. This study was performed to determine whether the newly syn thesized desmuramyl N-acyl dipeptides LK 409 and LK 410 were also capa ble of affecting the immune system. For this purpose, the peritoneal m acrophages were incubated in vitro with these two agents and TNF-alpha production was measured. In addition, the effect of LK 409 and LK 410 on TNF-alpha and IL-1 RNA levels in in vivo stimulated macrophages wa s determined by quantitative polymerase chain reaction (RT-PCR). None of the LK 409 and LK 410 concentrations tested were able to render mac rophages in vitro to excrete a detectable amount of TNF-alpha in the s upernatant fluid. However, the TNF-alpha and IL-1 RNA levels in macrop hages of in vivo treated mice (C57Bl/6) were increased in comparison t o mock-treated mice. The results indicate that LK 409 and LK 410 are c apable of inducing an increase in TNF-alpha and IL-1 RNA levels, yet i n vitro TNF-alpha production remains under detectable levels (40 U/ml) .