Central CO-heme oxygenase pathway raises body temperature by a prostaglandin-independent way

Recently, the carbon monoxide (CO)-heme oxygenase pathway has been shown to play an important role in fever generation by acting on the central nervou s system, but the mechanisms involved have not been assessed. Thus the pres ent study was designed to determine whether prostagandins participate in th e rise in body temperature (T-b) observed after induction of the CO-heme ox ygenase pathway in the central nervous system. intracerebroventricular (ICV ) injection of heme-lysinate (152 nmol/4 pi), which is known to induce the CO-heme oxygenase pathway, caused an increase in Th [thermal index (TI) = 5 .3 +/- 0.5 degrees C h], which was attenuated by ICV administration of the heme oxygenase inhibitor ZnDPBG (200 nmol/4 mu l; TI = 2.5 +/- 1.7 degrees C h; P < 0.05). No change in T-b was observed after intraperitoneal injecti on of the cyclooxygenase inhibitor indomethacin (5 mg/kg), whereas indometh acin at the same dose attenuated the fever induced by ICV administration of lipopolysaccharide (LPS) (10 ng/2 mu l) (vehicle/LPS: TI = 4.5 +/- 0.5 deg rees C h; indomethacin/LPS: TI = 1.7 +/- 1.0 degrees C h; P < 0.05). Intere stingly, indomethacin did not affect the rise in T-b induced by heme-lysina te (152 nmol/4 pi) ICV injection (vehicle/heme: TI = 4.5 +/- 1.4 degrees C h; indomethacin/heme: TI = 4.2 +/- 1.0 degrees C h). Finally, PGE(2) (200 n g/2 mu l) injected ICV evoked a rise in T-b that lasted 1.5 h. The heme oxy genase inhibitor ZnDPBG (200 nmol/4 mu l) failed to alter PGE(2)-induced fe ver. Taken together, these results indicate that the central CO-heme oxygen ase pathway increases T-b independently of prostaglandins.