title: Involvement of CRH in fever induced by a distinct pre-formed pyrogenic factor (PFPF).
abstract: 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.
  
  
  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.
authors.affiliation: Lab. Farmacologia, Fac. Ciências Farmacêuticas de Ribeirão Preto, SP, Brasil.
authors.forename: A R
authors.initials: AR
authors.lastname: Zampronio
authors.forename: M C
authors.initials: MC
authors.lastname: Melo
authors.forename: S J
authors.initials: SJ
authors.lastname: Hopkins
authors.forename: G E
authors.initials: GE
authors.lastname: Souza
mesh_terms: D000818:Animals; D054407:Chemokine CCL4; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D005334:Fever / Q000209:etiology*; D007213:Indomethacin / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D011749:Pyrogens / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054407:Chemokine CCL4; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D011749:Pyrogens; D014409:Tumor Necrosis Factor-alpha; D003346:Corticotropin-Releasing Hormone; D007213:Indomethacin