Increased in vitro production of interleukin 6 in response to trimethoprimamong persons with trimethoprim induced systemic adverse reactions

Objective. Trimethoprim occasionally triggers a systemic adverse reaction i ncluding fever, malaise, head and backache, and even overt meningeal irrita tion, particularly in women with an autoimmune rheumatic disease. To study the unknown pathogenesis of the reaction we measured the effect of trimetho prim upon the cytokine [interleukin (IL) 2, 6, 10, and tumor necrosis facto r-alpha] production of trimethoprim reactive and tolerant persons' peripher al blood mononuclear cells in vitro. Methods, Peripheral blood mononuclear cells from 12 women reactive to trime thoprim (3 with primary Sjogren's syndrome, 3 with systemic lupus erythemat osus, 1 with systemic scleroderma, 5 with no rheumatic disease) were cultur ed in the presence of trimethoprim, and the cytokine production was measure d, Eleven women who tolerated trimethoprim (6 with Sjogren's syndrome and 5 with no rheumatic disease) served as controls. Results. Therapeutic trimethoprim concentration induced in the mononuclear cells of the trimethoprim reactive patients significantly higher IL-6 produ ction [mean +/- SD (median), 2034 +/- 2965 (572) pg/ml] versus cells of the trimethoprim tolerant subjects [954 +/- 2552 (89) pg/ml; p = 0.036], No si gnificant differences in the production of other cytokines were detected. Conclusion. Trimethoprim induces IL-6 production in the peripheral blood mo nonuclear cells of trimethoprim reactive persons. We suggest that IL-6 prod uction is the probable trigger leading to the clinical reaction.