Drugs that induce systemic lupus erythematosus inhibit complement component C4.
The syndrome resembling systemic lupus erythematosus (SLE) associated with long-term treatment with hydralazine and isoniazid seems to be due to the drugs themselves rather than their metabolites. This syndrome is associated with deposition of immune complexes; and in the complement system inhibition of C4 is likely to increase deposition of immune complexes. In vitro, hydralazine and isoniazid inhibited 50% of the binding of C4 at 840 mumol/l and 1.05 mmol/l, respectively--ie, within the concentration ranges that have been used in therapy. Acetylated metabolites were not inhibitory at the maximum concentrations tested; and iproniazid, which does not cause SLE, gave 50% inhibition only at a concentration far exceeding that used in therapy.
D000107:Acetylation; D003181:Complement C4 / Q000037:antagonists & inhibitors*; D003171:Complement Pathway, Classical / Q000187:drug effects; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D007490:Iproniazid / Q000494:pharmacology; D007538:Isoniazid / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology; D010659:Phenylhydrazines / Q000494:pharmacology*
D003181:Complement C4; D010659:Phenylhydrazines; D006830:Hydralazine; D007490:Iproniazid; D007538:Isoniazid