title: Poisons and fever.
abstract: 1. Dysfunction of the thermoregulatory system is one of many pathologies documented in experimental animals and humans exposed to toxic chemicals. The mechanism of action responsible for many types of poison-induced fevers is not understood. Some elevations in body temperature are attributed to the peripheral actions of some poisons that stimulate metabolic rate and cause a forced hyperthermia. Exposure to organophosphate (OP) pesticides and certain metal fumes appears to cause a prolonged, regulated elevation in body temperature (Tb). 2. Activation of cyclo-oxygenase (COX) and the production of prostaglandin (PG)E2 in central nervous system (CNS) thermoregulatory centres is required to elicit a fever. Activating the COX-PGE2 pathway by a poison may occur by one of three mechanisms: (i) induction of cell-mediated immune responses and the subsequent release of cytokines; (ii) induction of lipid peroxidation in the CNS; and (iii) direct neurochemical activation. 3. Radiotelemetric monitoring of core temperature in unstressed rodents has led to an experimental animal model of poison-induced fever. Rats administered the OP agents chlorpyrifos and diisopropyl fluorophosphate display an initial hypothermic response lasting approximately 24 h, followed by an elevation in diurnal core temperature for 24-72 h after exposure. The hyperthermia is apparently a result of the activation of the COX-PGE2 pathway because it is blocked by the anti-pyretic sodium salicylate. Overall, the delayed hyperthermia resulting from OP exposure involves activation of thermoregulatory pathways that may be similar to infection-mediated fever.
authors.affiliation: Neurotoxicology Division, National Health Effects and Environmental Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. GORDON@HERL45.HERL.EPA.GOV
authors.forename: C J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: P J
authors.initials: PJ
authors.lastname: Rowsey
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D005334:Fever / Q000503:physiopathology*; D006801:Humans; D009943:Organophosphorus Compounds / Q000633:toxicity; D011042:Poisons
chemical_list: D009943:Organophosphorus Compounds; D011042:Poisons