Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF)

Objective: This study investigated the role of corticotrophin-releasing hormone (CRH) in mediating the fever induced by a novel pre-formed pyrogenic factor (PFPF), using a CRF antagonist in vivo and evaluating the capacity of PFPF to stimulate CRH release from the hypothalamus in vitro. Materials and Methods: Male Wistar rats were used. The PFPF, induced following brief incubation of rat peritoneal macrophages with LPS and retained on 10 or 20 kDa MW cut-off membranes, was injected intracerebroventricularly. Fever was monitored using a rectal probe. Hypothalamus tissue was incubated with PFPF to establish its ability to induce CRH release. The CRH was measured by ELISA. Results: PFPF induced a dose-dependent fever that was abolished by boiling or pronase treatment. Whereas both dexamethasone and indomethacin were effective in reducing interleukin- (IL) 1β-induced fever, only dexamethasone abolished the fever induced by PFPF. The CRH antagonist, α-helical CRH_9-41, abolished the fever induced by synthetic CRH, IL-8 and PFPF but not tumour necrosis factor-α (TNF-α). Like IL-1, PFPF was able to induce the release of CRH from rat hypothalamic tissue in vitro. Conclusions: These results suggest that the fever induced by PFPF depends on CRH release but not prostaglandin synthesis.