Stimulation of the hypothalamo-pituitary-adrenal axis by compounds formed in inflamed tissue.

1 Rat paws were injected with carrageenin, and their subcutaneous tissue perfused 135 min later. These perfusates were injected intravenously into receptor rats in which they caused an attenuation of inflammatory responses. 2 The effect was not observed in adrenalectomized receptor rats nor in receptors with electrolytic lesions in the median eminence of the hypothalamus but persisted in adrenal-demedullated animals. 3 The active perfusates also induced eosinopenia in normal or adrenal-demedullated animals, but not in adrenalectomized rats, and produced an increase in blood corticosterone with a concomitant decrease in the amounts of adrenal ascorbic acid. 4 The active perfusates did not affect the responses of isolated preparations to histamine, bradykinin, prostaglandins and 5-hydroxytryptamine neither did they elicit changes of the arterial blood pressure in receptor animals. 5 The anti-inflammatory activity present in perfusates from inflamed paws seems to be formed slowly at the site of the developing inflammatory reaction, since perfusates collected 30-65 min after the injection of carrageenin were ineffective, as was plasma taken from donor rats at various time intervals after carrageenin injections. 6 It is suggested that the anti-inflammatory factor present in the active perfusates exerts its action by stimulation of the hypothalamo-pituitary-adrenal axis.