Abstract-Mixed lymphocytes reactions (MLR) and concanavalin A (Con A) or phytohemagglutinin (PHA)-stimulated proliferative responses were dose-depend ently inhibited by salazosulfapyridine (SASP) and cyclosporin A (CsA) in the con centration 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 subse quent 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.
Salazosulfapyridine (SASP) was first reWe have already reported that SASP has a ported by Svartz (1) to be effective in the marked inhibitory effect on in vitro produc treatment of rheumatoid arthritis (RA). A high tion of antibodies, suggesting that its inhibi incidence of adverse effects such as nausea, tory effect was mediated by T cells (8) . In anorexia, dispesia and abdominal pain was addition, it was found that interleukin 2 (IL-2) reported by Scinclair and Duthie (2); since production stimulated with sheep red blood then, SASP has been used for maintenance cells (SRBC) was also inhibited by SASP. therapy of ulcerative colitis rather than for RA. Recently, we have found that SASP inhibits Thereafter, McConkey et al. (3) reevaluated the anti-DNA antibody production in auto the effectiveness of SASP in RA and papers immune mice (manuscript is in preparation). appeared describing that SASP has an anti Cyclosporin A (CsA), a fungal cyclic rheumatic effect comparable to those of D polypeptide, is an immunosuppressive agent penicillamine and gold compounds (4, 5). used as a rejection inhibitor in organ trans Moreover, the effect of SASP was evaluated plantation, which acts principally by inhibit in experiments using animal models (6, 7), ing T cell functions. In particular, much infor but the mechanism underlying the anti mation is available concerning the effect of rheumatic effect of SASP remains unclear. CsA on IL-2 production and IL-2 receptor (R) Accordingly, it is important to elucidate the expression (9-13). In this study, the effects immunopharmacological action of SASP.of SASP on the proliferation and IL-2 produc tion induced by alloantigen, concanavalin A