ABSTRACT
The pyrogenic interferon inducer polyinosinic: polycytidylic acid (Poly I: C) was shown to stimulate rises in both prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in conscious rabbits in vivo. Poly I:C (2·5 μg/kg) stimulated a fivefold rise in circulating immunoreactive (ir) PGE2, with a lag phase of 60 min, which was sustained during the subsequent 4-h period of observation. Poly I:C also stimulated a 2·5-fold rise in circulating irPGF2α with a lag phase of 90 min, which was followed by a return to basal levels after 5 h. The rises in circulating irPGE2 and irPGF2α stimulated by Poly I:C were prevented by pretreatment with the non-steroidal anti-inflammatory drug ketoprofen. Both the irPGE2 and irPGF2α responses to Poly I:C (2·5 μg/kg, i.v.) were antagonized by the corticotrophin-releasing factor-41 (CRF-41) receptor antagonist (α-helical CRF (9–41), 25 μg/kg, i.v.) administered 5 min prior to the pyrogen. Peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001, 2·5 mg/kg, i.v.) administered 5 min prior to the pyrogen, also inhibited both the PGE2 and PGF2α responses to Poly I:C (2·5 μg/kg, i.v.). However, control mouse IgG also inhibited the PGE2 response. In conclusion, these results suggest a modulatory role for endogenous peripheral CRF-41 in the circulating prostaglandin responses to the pyrogen Poly I: C and this effect may be responsible for the antipyretic actions of peripherally administered CRF-41 antagonists and antibodies.
Journal of Endocrinology (1993) 138, 7–11
S88 The viral mimic polyinosinic: polycytidylic acid (Poly I:C) induces TRPA1 channel hyper-responsiveness in an adult human stem cell-derived sensory neuronal model
