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Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF)
A R Zampronio1, M C Melo, S J Hopkins
1Lab. Farmacologia, Fac. Ciências Farmacêuticas de Ribeirão Preto, SP, Brasil.
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) 1beta-induced fever, only dexamethasone abolished the fever induced by PFPF. The CRH antagonist, a-helical CRH9-41, abolished the fever induced by synthetic CRH, IL-8 and PFPF but not tumour necrosis factor-a (TNF-alpha). 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.