A possible role for endogenous peripheral corticotrophin‐releasing factor‐41 in the febrile response of conscious rabbits.

1. The actions of peripheral corticotrophin‐releasing factor‐41 (CRF‐41) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic.polycytidylic acid (poly(I).poly(C)) have been studied using a CRF‐41 receptor antagonist (alpha‐helical CRF(9‐41) and anti‐CRF‐41 monoclonal antibodies. 

2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.), or for central CRF‐41 antagonism experiments, via an indwelling third ventricle cannula (I.C.V.). Blood samples were taken at time intervals from a marginal ear vein and plasma cortisol levels determined by radioimmunoassay. 

3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated a reproducible biphasic rise in body temperature with a lag phase of 45‐60 min and peaks at 90 and 225 min. 4. The febrile response to poly(I).poly(C) (2.5 micrograms/kg I.V.) was antagonized by blockade of peripheral CRF‐41 actions using either monoclonal anti‐CRF‐41 antibodies (2.5 mg/kg i.v.) or the CRF‐41 receptor antagonist (alpha‐helical CRF(9‐41); 25 micrograms/kg i.v.) administered 5 min prior to the pyrogen. 5. Centrally administered CRF‐41 receptor antagonist (2.5 micrograms/kg I.C.V.) failed to affect the febrile response to poly(I).poly(C) (2.5 micrograms/kg i.v.). 6. CRF‐41 immunoneutralization after the onset of temperature rises caused an immediate and significant defervescence. 7. In conclusion, these results suggest a modulatory pro‐pyretic role for endogenous peripheral CRF‐41 in the febrile responses to poly(I).poly(C).