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.