Delayed febrile effects of chlorpyrifos: is there cross-tolerance to bacterial lipopolysaccharide?

Abstract

Oral chlorpyrifos (CHP) induces hypothermia followed by a fever that persists for several days in the rat. To understand the neuro-immune mechanisms of CHP-induced fever, we compared the tolerance and cross-tolerance between CHP and the fever elicited by lipopolysaccharide (LPS) ( Escherichia coli). Female rats were administered the corn oil (CO) vehicle 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 reduction in T c followed by an elevation the next day after each CHP treatment. The day after the last CHP treatment, rats were administered saline or 50 μg/kg LPS (i.p.). CHP-treated rats had a smaller LPS fever that was attributed to their elevated baseline T c. In another study, rats were dosed with saline or LPS daily for three days. By the time of the third LPS injection there was no febrile response, indicating 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 accentuated hypothermic and febrile response to CHP. Plasma cholinesterase activity was unaffected by repeated LPS treatment, suggesting that the metabolism of CHP in the liver was unaffected by LPS. Overall, the neural-immune mechanisms for LPS fever is distinct from that of CHP in view of marked difference in mechanisms of tolerance.