Tumor necrosis factor is involved in chlorpyrifos-induced changes in core temperature in the female rat

Chlorpyrifos (CHP), an OF-based pesticide, induces hypothermia in the rat f ollowed by a fever that persists for several days. The cytokine, tumor necr osis factor-alpha (TNF), is induced by lipopolysaccharide (LPS) and release d during fever and has both pyrogenic and cryogenic (i.e. antipyretic) prop erties. Administering antibodies to TNF (anti-TNF) is known to disrupt feve r from infection. Thus, the purpose of this study was to examine whether an ti-TNF also disrupts CHP-induced changes in body temperature of the female Long-Evans rat. A positive effect would suggest a role of TNF in the etiolo gy of OF toxicity. In study one, rats were given either saline or anti-TNF (50 000 units, ip). Three hours later, animals were given corn oil (CO) or 25 mg/kg CHF by oral gavage in the morning. In study two, rats were given a nti-TNF followed by CO or 10 mg/kg CHP in the afternoon. Core temperature a nd motor activity were monitored continuously by telemetry. In study one, a nti-TNF (50 000 units) had no effect on the hypothermic response to 25 mg/k g CHP. However, anti-TNF treated animals maintained higher fevers 3 days (4 8-96 h post-injection) after CHP treatment. In study two, anti-TNF attenuat ed the hypothermic response induced by 10 mg/kg CHP but had no effect on th e magnitude of the delayed fever. Overall, 25 mg/kg CHP elicited a longer p eriod of hypothermia and delayed fever compared to 10 mg/kg CHP. Anti-TNF p retreatment attenuated the hypothermic response at the lower CHP dose and e xacerbated the fever at the higher CHF dose. Anti-TNF also attenuated the h ypothermic effect of high doses of LPS and exacerbated LPS-induced fever. T hese data indicate that endogenously produced TNF is involved in the etiolo gy of CHP mediated hypothermia and fever. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.