IN-VITRO TNF-ALPHA PRODUCTION AND IN-VIVO ALTERATION OF TNF-ALPHA RNAIN MOUSE PERITONEAL-MACROPHAGES AFTER TREATMENT WITH DIFFERENT BACTERIAL DERIVED AGENTS
S. Novakovic et I. Boldogh, IN-VITRO TNF-ALPHA PRODUCTION AND IN-VIVO ALTERATION OF TNF-ALPHA RNAIN MOUSE PERITONEAL-MACROPHAGES AFTER TREATMENT WITH DIFFERENT BACTERIAL DERIVED AGENTS, Cancer letters, 81(1), 1994, pp. 99-109
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)
.