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The pannus of rheumatoid arthritis is a proliferating mass of various cells and tissues, including follicles of lymphoid cells, and is the major agent of destruction of the surrounding structural tissues. Infiltrating lymphocytes are thought to be the prime stimuli for the growth of the pannus, through the secretion of lymphokines. In contrast to this high turnover, destructive rheumatoid granuloma, most commonly used experimental granuloma models are of the non-immune, low turnover variety and thus give a rather poor reflection of clinical conditions. A model has been developed in our laboratory in which lymph node cells are removed from Freund's complete adjuvant sensitized rats and injected into sponge implants in normal syngeneic recipient animals, leading to enhancement of granuloma formation. This response has been characterized and shown to be related to lymphocyte activation and to the sensitivity of rats to polyarthritis induction. The lymphocyte transfer model may be useful in studying the action of drugs on lymphocyte-mediated chronic inflammatory responses and the principle of lymphocyte transfer may be applied to other hypersensitivity granuloma models.

We are currently characterizing different macrophage sub-populations according to their release of oxygen free radicals (measured as chemiluminescence) under various stimuli and their responses to drugs and mediators. Mouse macrophages were obtained by peritoneal or lung lavage and stimulatedin vitro with opsonized zymosan (OpZ) or the calcium ionophore A23187. Chemiluminescence was measured in a luminometer and resonses obtained after 5 min expressed as percentages of standard responses to the stimuli. Almost identical dose-response curves to OpZ were obtained with peritoneal and alveolar macrophages, while the dose-response curve of peritoneal macrophages to A23187 was much shallower. The response to A23187 was generally much weaker than that to OpZ and in both types of macrophages PGE2 was a more effective inhibitor of OpZ-induced chemiluminescence than of that inducd by A23187. The response to OpZ in peritoneal macrophages was inhibited in a dose-related manner by both PGE2 and superoxide dismutase, but not by indomethacin,d-penicillamine, piroxicam or phenylbutazone. OpZ but not A23187, is a suitable stimulus for pharmacological studies on macrophage chemiluminescence.