Hydralazine and isoniazid reduce the formation of soluble immune complexes by complement.
Hydralazine and isoniazid reduce the covalent binding capacity of C4. Since these two drugs are known to induce a systemic lupus erythematosus (SLE)-like syndrome, it has been suggested that this reduced binding could lead to the abnormal processing of immune complexes in vivo. Complement mediated solubilization and inhibition of immune precipitation were tested in vitro in normal human serum exposed to various concentrations of the two drugs. The formation of soluble immune complexes in the assays was reduced. The concentrations needed to induce a significant decrease were (a) for solubilization: 50 mM hydralazine and 25 mM isoniazid, and (b) for inhibition of immune precipitation: 50 mM of both. Such concentrations are unlikely to be present in vivo, so that the induction of SLE by these two drugs cannot be explained exclusively by reduced formation of soluble complexes by complement.
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007538:Isoniazid / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology
D000936:Antigen-Antibody Complex; D003176:Complement C3; D003181:Complement C4; D006830:Hydralazine; D003165:Complement System Proteins; D007538:Isoniazid