MODULATION OF THE INFLAMMATORY RESPONSE BY CORTICOTROPIN-RELEASING FACTOR

Peptides of the corticotropin-releasing factor (CRF) family have been shown to have either pro- or anti-inflammatory activities. CRF (10-30 mu g/kg) administered subcutaneously or intravenously could inhibit ed ema and dye leakage in the rat paw produced by several injuries. These findings are opposed to some results suggesting a predominantly pro-i nflammatory effect of CRF mainly in arthritic processes. The purpose o f this work was to identify in vivo and in vitro the conditions for th e pro- or anti-inflammatory actions of CRF in order to clarify its phy siological and pharmacological function. Using the rat paw edema test we observed that only the highest doses of CRF employed (5 mu g) induc ed a moderate and sustained swelling. Pre-treatment with low doses of CRF (0.5-5 ng) was able to inhibit the edema induced by Naja naja naja phospholipase A(2), carrageenin or histamine. Higher doses (50 ng-5 m u g) had no anti-inflammatory activity. When co-injected with Naja naj a naja phospholipase A(2) or histamine the peptide did not modify the swelling at doses up to 500 ng, showing at 5 mu g an additive edema wi th Naja naja naja phospholipase A(2). In vitro, CRF did not modify the release of histamine but slightly increased the release of arachidoni c acid to the medium. Our findings show a clear dose dependence on the local effects of CRF in inflammatory responses. These results suggest that the mechanisms of the two dose-related phenomena may be distinct .