Abstract

Three phases of the response to a subcutaneously implanted cotton pellet in the acutely adrenalectomized rat have been described. These consist of 1) a transudative phase, defined as the increase in wet weight of the pellet which occurred during the first three hours, 2) an exudative phase, defined as leakage of Evans blue from the bloodstream around the granuloma and occurring between 3 and 72 hours after implanting the pellet and 3) a proliferative phase, measured as the increase in dry weight of the granuloma which occurs between three and six days after implantation. Daily estimation of the hydroxyproline contents of granulomas from one through six days after implantation of a cotton pellet confirmed the validity of using the increase in dry weight of the granuloma between days 3 and 6 as a measure of the proliferative phase. The effects of certain steroidal and nonsteroidal drugs and antagonists of endogenous permeability factors on the phases of the inflammatory response were examined. The potency of the antiinflammatory drugs against the exudative phase was dexamethasone > hydrocortisone > indomethacin. Flufenamic acid, at the doses used, failed to inhibit exudation of Evans blue into the region of the implant. Antagonists of histamine, serotonin and the kininforming system also failed to inhibit the exudative response to implantation of cotton pellets. The potency of the drugs against the proliferative phase was dexamethasone > indomethacin > hydrocortisone. Flufenamic acid inhibited a constant fraction of the proliferative weight increase at all doses used.