THE IMMUNOMODULATORY EFFECTS OF THE HERBICIDE PROPANIL ON MURINE MACROPHAGE INTERLEUKIN-6 AND TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION

Intraperitoneal tip) exposure to propanil (3,4-dichloropropionanilide) has previously been shown to affect macrophage cytotoxicity. In this study, we compared the immunotoxic effects of propanil, after differen t routes of in vivo administration, on cytokine production by thioglyc ollate-elicited peritoneal macrophages. C57B1/6 mice were treated with either vehicle or 200 mg/kg propanil ip, or with vehicle, 40, or 400 mg/kg propanil orally. Three or 7 days later, ex vivo production of in terleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by macr ophages after lipopolysaccharide OBS) stimulation was determined. Both oral and ip propanil exposure resulted in up to a 60-70% reduction in IL-6 and TNF-alpha production by the LPS-stimulated macrophages, depe nding on the route, postexposure time, and dose of propanil administer ed. Oral exposure to propanil also caused splenomegaly and thymic atro phy in animals in much the same manner as animals exposed via the ip r oute. In vitro exposure to propanil also significantly reduced macroph age cytokine production. Thioglycollate-elicited macrophages from norm al mice were cultured in the continuous presence of 0, 10, or 20 mu M propanil plus LPS. This exposure caused a significant reduction in IL- 6 and TNF protein production by these macrophages in a concentration-d ependent manner. Northern blot analysis demonstrated that the message levels of these cytokines were reduced by approximately the same perce ntage as the protein levels in propanil-treated macrophages, indicatin g a possible transcriptional or pretranscriptional target(s) for propa nil. (C) 1997 Academic Press.