INHIBITORY EFFECT OF 3,4-DICHLOROPROPIONANILINE ON CYTOKINE PRODUCTION BY MACROPHAGES IS ASSOCIATED WITH LPS-MEDIATED SIGNAL-TRANSDUCTION

Our previous studies demonstrated that both in vivo and in vitro 3,4-d ichloro-propionanilide (propanil) exposure inhibited interleukin-6 (IL -6) and tumor necrosis factor (TNF) production by adherent thioglycoll ate-elicited peritoneal cells (macrophages) after lipopolysaccharide ( LPS) stimulation. In this study, we report that IL-6 and TNF-alpha mes sage is reduced by propanil in a concentration-dependent pattern, yet the stability of cytokine mRNA is not affected, hn addition, exposure of macrophages to propanil after a relatively short period of LPS stim ulation significantly reduced the production of IL-6 and TNF, Determin ation of the intracellular Ca2+ levels demonstrates that LPS-induced C a2+ release is abrogated in propanil-treated macrophages, However, the binding of LPS to macrophages is not affected, Measurement of inosito l 1,4,5-triphosphate (IP3) demonstrates that propanil significantly in creases the level and the duration of IP3 in macrophages, These result s suggest that the inhibitory effect of propanil on macrophage cytokin e production is associated with the early stages of LPS-mediated signa l transduction in macrophages.