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Inflammatory processes may be suppressed by endogenous mechanisms such as release of adrenocorticosteroid hormones through stimulation of the hypothalamus-pituitary-adrenal axis. In the present study, the relationship between the temporal development of carrageenan-induced edema in the hindlimb of the rat and release in plasma of the principal endogenous adrenocorticosteroid of the rat corticosterone was investigated. Suplantar injection of carrageenan produced a biphasic increase in basal plasma corticosterone levels that was not attributed to diurnal variation. The plasma level of corticosterone increased rapidly after injection of carrageenan and peaked 12-fold at 20 min. This first phase increase was attributed to the stress of the injection since it was mimicked by subplantar injection of saline. The second phase of corticosterone release was gradual and peaked 12-fold 7 hr after injection of carrageenan. The second phase was not elicited by subplantar injection of saline. When the hypothalamus-pituitary-adrenal axis is impaired via hypophysectomy, carrageenan-induced edema is more intense and lasts longer than in control rats. The results demonstrate that adrenocorticosteroid hormones are released as a result of the stress of injection and by the inflammatory response. Release of adrenocorticosteroids acts as a feedback mechanism to suppress the inflammatory response.

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