Peripheral corticotropin-releasing factor mediates the elevation of plasma IL-6 by immobilization stress in rats.

We previously reported the elevation of plasma interleukin (IL)-6 activity in response to immobilization stress in rats. To investigate the role of peripheral corticotropin-releasing factor (CRF) in this response, we examined the effects of CRF antagonists on immobilization-induced IL-6 response. Intravenous pretreatment with either [D-Phe12,Nle21,38,CalphaMeLeu37]-anti-human rat (h/r) CRF12-41 (1.5 mg/kg) or cyclo(30-33)[D-Phe12, Nle21,38,Glu30, Lys33]-h/rCRF12-41 (Astressin, 0.5 mg/kg) attenuated the IL-6 response to immobilization, which confirmed our previous finding that systemic administration of an antiserum against CRF blocked this response. In addition, an intraperitoneal injection of h/rCRF (100 micrograms/kg) or rat urocortin (10 and 100 micrograms/kg) increased the plasma IL-6 activity, mimicking the response to immobilization. An intravenous injection of h/rCRF (100 micrograms/kg) also elevated plasma IL-6 in adrenalectomized rats. These findings suggest that peripheral CRF mediates the plasma IL-6 elevation in response to immobilization.