The central role of corticotropin-releasing hormone in stress-induced hyperthermia and LPS-induced fever in rats

AIM:To further investigate the role of central corticotropin-releasing hormone in stress-induced hyperthermia and lipopolysaccharide (LPS)-induced fever in the rat.METHODS:Test substances were administered intracerebroventricularly (icv) via a third ventricle cannula. Body temperature responses were monitored at 30 min intervals using colonic thermistor probes. Arginine vasopressin (AVP) level in the ventral septal area (VSA) determined by radioimmunoassay. RESULTS:In normal saline controls,rats were handled to take the colonic temperature,their body temperature significantly increased with a peak of(0.88±0.31)℃.The injection(icv)of α-helical CRH(9-41),a CRH-41 receptor antagonists,markedly attenuated the stress-induced hyperthermia within 90 min after injection of normal saline.LPS(300 ng,icv)stimulated a biphasic rise in the colonic temperature,the 3.5 h thermal response index(TRI_3.5)and AVP levels in the VSA of LPS-treated rats were higher than those of control rats.The AVP responses to LPS were inhibited significantly by blockade of central CRH actions using α-helical CRH(9-41)(5μg,icv)administered 10 min prior to LPS,whileα-helical CRH(9-41)(5μg,icv)resulted in exacerbated febrile responses to LPS(300 ng,icv). CONCLUSION:Central CRH plays an important role in stress-induced hyperthermia. The injection (icv) of α-helical CRH(9-41) enhances markedly LPS-induced fever in rats. CRH is a dual action molecule in LPS-induced fever, which itself mediates LPS-induced fever, at the same time, and limits the rise in body temperature during fever through actions of AVP in the VSA and glucocoticoids.