Augmentation of concanavalin A-induced immunosuppression by indomethacin.
These studies show that, in BALB/C mice, when antibody synthesis against sheep red blood cells is suppressed by concanavalin A, treatment with indomethacin (4-8 mg/kg per os) will augment this suppression. Two other nonsteroidal anti-inflammatory drugs, flufenamic acid and meclofenamic acid (50 mg/kg), also have this effect, whereas phenylbutazone was inactive at this dose. The augmentation of concanavalin A-induced immunosuppression by indomethacin could not be demonstrated on the response to the T-independent antigen polyvinypyrrolidone. In contrast to indomethacin, which inhibits cyclooxygenase, neither nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, nor eicosa-5,8,11,14-tetraynoic acid, an inhibitor of both the cyclooxygenase and the lipoxygenase pathways, had this augmenting effect. Therefore, we do not have strong evidence that the absence of a prostaglandin is responsible for the effect of indomethacin. However, inhibition of the pathway leading to prostaglandin synthesis causes an increase in arachidonic acid metabolism via the lipoxygenase pathway. A product of this pathway, such as a leukotriene, may have immunosuppressive effects in this model. Evidence for the enhancement of a suppressor cell population is provided by an in vitro coculture assay. Cells treated with concanavalin A and indomethacin had more suppressive activity than cells treated with concanavalin A or indomethacin alone.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D007166:Immunosuppressive Agents; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D007166:Immunosuppressive Agents; D003208:Concanavalin A; D007213:Indomethacin