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J Appl Physiol 88: 1607-1613, 2000;
8750-7587/00 $5.00
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Vol. 88, Issue 5, 1607-1613, May 2000

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

Alexandre A. Steiner and Luiz G. S. Branco

Faculdade de Odontologia and de Medicina de Ribeirão Preto, Universidade de São Paulo, 14040-904 Ribeirão Preto, São Paulo, Brazil

Recently, the carbon monoxide (CO)-heme oxygenase pathway has been shown to play an important role in fever generation by acting on the central nervous system, but the mechanisms involved have not been assessed. Thus the present study was designed to determine whether prostagandins participate in the rise in body temperature (Tb) observed after induction of the CO-heme oxygenase pathway in the central nervous system. Intracerebroventricular (ICV) injection of heme-lysinate (152 nmol/4 µl), which is known to induce the CO-heme oxygenase pathway, caused an increase in Tb [thermal index (TI) = 5.3 ± 0.5°C · h], which was attenuated by ICV administration of the heme oxygenase inhibitor ZnDPBG (200 nmol/4 µl; TI = 2.5 ± 1.7°C · h; P < 0.05). No change in Tb was observed after intraperitoneal injection of the cyclooxygenase inhibitor indomethacin (5 mg/kg), whereas indomethacin at the same dose attenuated the fever induced by ICV administration of lipopolysaccharide (LPS) (10 ng/2 µl) (vehicle/LPS: TI = 4.5 ± 0.5°C · h; indomethacin/LPS: TI = 1.7 ± 1.0°C · h; P < 0.05). Interestingly, indomethacin did not affect the rise in Tb induced by heme-lysinate (152 nmol/4 µl) ICV injection (vehicle/heme: TI = 4.5 ± 1.4°C · h; indomethacin/heme: TI = 4.2 ± 1.0°C · h). Finally, PGE2 (200 ng/2 µl) injected ICV evoked a rise in Tb that lasted 1.5 h. The heme oxygenase inhibitor ZnDPBG (200 nmol/4 µl) failed to alter PGE2-induced fever. Taken together, these results indicate that the central CO-heme oxygenase pathway increases Tb independently of prostaglandins.

temperature; fever; lipopolysaccharide; cyclooxygenase; prostaglandin H synthase; indomethacin; central nervous system


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