Increased in vitro production of interleukin 6 in response to trimethoprim among persons with trimethoprim induced systemic adverse reactions.
OBJECTIVE
Trimethoprim occasionally triggers a systemic adverse reaction including fever, malaise, head and backache, and even overt meningeal irritation, particularly in women with an autoimmune rheumatic disease. To study the unknown pathogenesis of the reaction we measured the effect of trimethoprim upon the cytokine [interleukin (IL) 2, 6, 10, and tumor necrosis factor-alpha] production of trimethoprim reactive and tolerant persons' peripheral blood mononuclear cells in vitro.


METHODS
Peripheral blood mononuclear cells from 12 women reactive to trimethoprim (3 with primary Sjögren's syndrome, 3 with systemic lupus erythematosus, 1 with systemic scleroderma, 5 with no rheumatic disease) were cultured in the presence of trimethoprim, and the cytokine production was measured. Eleven women who tolerated trimethoprim (6 with Sjögren'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 production [mean +/- SD (median), 2034+/-2965 (572) pg/ml] versus cells of the trimethoprim tolerant subjects [954+/-2552 (89) pg/ml; p = 0.036]. No significant differences in the production of other cytokines were detected.


CONCLUSIONS
Trimethoprim induces IL-6 production in the peripheral blood mononuclear cells of trimethoprim reactive persons. We suggest that IL-6 production is the probable trigger leading to the clinical reaction.
Antonen
J
J
Department of Medicine, Tampere University Hospital, Medical School, University of Tampere, Finland. jaakko.antonen@uta.fi
Saha
H
H
Hulkkonen
J
J
Lumio
J
J
Pasternack
A
A
Hurme
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000382:microbiology; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000382:microbiology; D014295:Trimethoprim / Q000009:adverse effects*
D000892:Anti-Infective Agents, Urinary; D015850:Interleukin-6; D014295:Trimethoprim