Inhibition of proliferative responses and interleukin 2 productions by salazosulfapyridine and its metabolites.

Mixed lymphocytes reactions (MLR) and concanavalin A (Con A)- or phytohemagglutinin (PHA)-stimulated proliferative responses were dose-dependently inhibited by salazosulfapyridine (SASP) and cyclosporin A (CsA) in the concentration ranges of 1 x 10(-5) -5 x 10(-4) M and 10-1000 ng/ml, respectively. Such a significant inhibition was not observed with metabolites of SASP, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA). In addition, SASP and CsA inhibited the production of interleukin 2 (IL-2) from splenocytes in these experiments. The inhibitory effect of CsA on IL-2 production practically correlated with that on proliferative responses, whereas SASP showed a less marked inhibitory effect on IL-2 production than on proliferative responses. Neither SP nor 5-ASA inhibited the IL-2 production. In the Con A-induced proliferative response, SASP showed a full inhibition even when added after 4-8 hr of culture, but CsA did not. The splenocytes that were pulsed with Con A for 4 hr could proliferate in response to Con A-supernatant or purified IL-2. CsA exhibited the inhibitory activity only when present during the time of Con A-pulsing, while SASP acted on the subsequent stage of the response, exerting its inhibitory effect. These findings suggest that SASP down-regulates the immune response by a mechanism apparently distinct from that of CsA.