Persistent inflammatory responses enhance the proinflammatory activity of lymphocytes

Abstract

Intravenous administration to leucopenic rats of lymphocyte suspensions, or lymphocyte products, restored the depressed inflammatory responses of these animals to various inflammatory stimuli. Utilizing carrageenin to induce inflammatory responses in leucopenic animals, an enhanced restorative effect of lymphocytes, or of their products, was observed when the cells were collected from donor rats in which a persistent inflammatory lesion was previously induced in the paw by the local injection of complete Freund's adjuvant (CFA). The enhancement of cell activity was gradual with the age of the lesion: cells collected from donors bearing 3-day-old lesions were less effective than cells from donors in which the persistent inflammatory lesion was induced 18 days before. Steroidal and non-steroidal anti-inflammatory drugs (e.g. hydrocortisone, aspirin, sodium salicylate and indomethacin), administered to donor animals, were capable of blocking the restorative effect of lymphocytes. This blocking action affected also cells rendered hyperactive by the stimulus of CFA-induced lesions, but was reverted by the interruption of drug administration to donors. When cells rendered inactive by the action of anti-inflammatory drugs were disrupted before injection into leucopenic animals, the resulting cell products were capable of restoring the depressed inflammatory responses of these animals to carrageenin. Aspirin was an exception, because it rendered inactive the cell products besides the intact cells. It is concluded that persistent inflammatory responses induced by CFA enhance the proinflammatory function of lymphocytes in the rat which, in turn, might contribute to the persistency of the response. Antiinflammatory drugs may interrupt this sort of vicious circle by decreasing the amounts of the available active cell products.