Role of anterior hypothalamic natriuretic peptide in lipopolysaccharide-induced fever in rats

We investigated whether within the preoptic area, natriuretic peptide (NP) acts as an endogenous antipyretic in rats made febrile by systemic administration of bacterial endotoxin (lipopolysaccharide, LPS). Intravenous (i.v.) injection of LPS (2 μg/kg) induced a triphasic fever. The third phase of this fever was (a) significantly enhanced by an intrapreoptic (i.p.o.) injection of the NP-receptor (A-type and B-type) antagonist HS-142-1(1 μg), and (b) significantly attenuated by an i.p.o. injection of atrial NP (ANP, 20 ng). When given i.v., LPS induced significant upregulation of the mRNA coding for C-type NP within the anterior hypothalamus, and tended to upregulate that for ANP. The anterior hypothalamic expression of interleukin-1β mRNA was significantly greater in rats injected i.v. with LPS than in saline-injected rats. These results suggest that NPs produced within the anterior hypothalamus after i.v. injection of LPS may act upon preoptic NP receptors to inhibit the LPS-induced fever, possibly through attenuation of the LPS-induced production of proinflammatory cytokines and/or the subsequent final fever mediator prostaglandin E2.