Fever induced by platelet-derived growth factor, in contrast to fever induced by lipopolysaccharide, depends only on nitric oxide, but not on carbon monoxide pathway

Abstract

Platelet-derived growth factor (PDGF) is a multifunctional protein which is known to induce a febrile response when injected intracerebroventricularly. The gaseous neurotransmitters, nitric oxide (NO) and carbon monoxide (CO), are both known to exert thermoregulatory effects and to participate in lipopolysaccharide-induced fever. In this study, we investigated the role of NO and CO in the febrile response to PDGF-BB in rats. Intracerebroventricular (i.c.v.) injection of PDGF-BB produced a dose-dependent increase in body temperature. This increase in body temperature induced by PDGF-BB was exacerbated by N G-nitro- l-arginine methyl ester ( l-NAME—a nonselective NO synthase inhibitor) and S-methyl- l-thiocitrulline treatment [SMTC—a neuronal NOS (nNOS) selective inhibitor], but not by aminoguanidine treatment [an inducible NOS (iNOS) selective inhibitor]. Zinc deuteroporphyrin 2,4-bis glycol treatment (ZnDPBG—a nonselective heme oxygenase (HO) blocker) did not affect PDGF-BB fever. Our data indicate that the NO but not the CO pathway participates in PDGF-BB fever. Furthermore, our data show that nNOS is the NOS isoform responsible for NO synthesis in this response.