Corticotropin-releasing factor inhibits thermal injury

Thermal injury to the skin increases transfer of plasma fluids and proteins into the interstitium. Here, protein extravasation and edema were produced by immersion of the anesthetized rat's paw in 48 degrees C or 58 degrees C water for 5 min. Protein extravasation was measured by Evans blue dye leakage into the skin and edema by increases in skin weights. Corticotropin-releasing factor (CRF), having the human/rat 41-amino acid sequence, was efficacious in reducing these indices of thermal injury. Injected i.v. at microgram doses or intradermally at nanogram doses, it inhibited the protein extravasation and edema produced by heat. The intradermal median inhibitory dose (ED50) of CRF against protein extravasation elicited by 48 degrees C water was 21.8 times lower than the i.v. ED50, indicating that CRF's actions occurred locally in the paw skin. Ovine-CRF and dynorphin A(1-13) injected i.v. inhibited the protein extravasation and edema induced by 58 degrees C water, but morphine, ethylketocyclazocine and FK 33,824 (a stabilized enkephalin analog) were not active at this temperature. CRF may be a powerful inhibitor of the acute inflammatory response of the skin to thermal irritation.