DELAYED FEBRILE EFFECTS OF CHLORPYRIFOS - IS THERE CROSS-TOLERANCE TOBACTERIAL LIPOPOLYSACCHARIDE

Oral chlorpyrifos (CHP) induces hypothermia followed by a fever that p ersists for several days in the rat. To understand the neuro-immune me chanisms of CHP-induced fever, we compared the tolerance and cross-tol erance between CHP and the fever elicited by lipopolysaccharide (LPS) (Escherichia coli). Female rats were administered the corn oil (CO) ve hicle or CHP (10 mg/kg; po) daily for 4 days while core temperature (T -c) and motor activity (MA) were monitored by telemetry. There was a r eduction in T-c followed by an elevation the next day after each CHP t reatment. The day after the last CHP treatment, rats were administered saline or 50 mu g/kg LPS (i.p.). CHP-treated rats had a smaller LPS f ever that was attributed to their elevated baseline T-c. In another st udy, rats were dosed with saline or LPS daily for three days. By the t ime of the third LPS injection there was no febrile response, indicati ng tolerance to LPS. Rats were then dosed with CO or CHP (10 mg/kg) 24 h after the third LPS treatment. LPS-tolerant rats displayed an accen tuated hypothermic and febrile response to CLIP. Plasma cholinesterase activity was unaffected by repeated LPS treatment, suggesting that th e metabolism of CHP in the liver was unaffected by LPS. Overall, the n eural-immune mechanisms for LPS fever is distinct from that of CHP in view of marked difference in mechanisms of tolerance. (C) 1998 Elsevie r Science Ireland Ltd. All rights reserved.