Changes in T and B lymphocyte proliferative responses in adjuvant-arthritic rats: antagonism by indomethacin

The effects of a potent non-steroidal antiinflammatory drug, indomethacin, on the inflammatory response and lymphocyte proliferation were investigated in adjuvant-arthritic rats. As shown by others, adjuvant produced a time-dependent swelling of the contralateral paw which was maximal within 14 days after administration. Upon the intraperitoneal injection of either 1 or 2 mg/kg of indomethacin, twice daily for 3 days, the swelling of the contralateral paw was completely reduced. Selective changes in proliferative responses of splenic T and B lymphocytes to mitogens were found to accompany these effects. Adjuvant arthritic rats were found to have increased T cell proliferation when stimulated with phytohemagglutinin, whereas proliferation of B lymphocytes in the presence of lipopolysaccharide was completely suppressed. Indomethacin treatment at either the 1 or 2 mg/kg dose was found to depress the proliferative responses of T cells by 60 and 95%, respectively. In contrast, the hyporesponsiveness of B lymphocytes in arthritic animals was partially reversed with 2 mg/kg indomethacin. These results suggest that indomethacin may be exerting an antiinflammatory effect through a selective alteration of T and B lymphocyte activities in lymphoid tissue.