The effects of
sulfones and
sulfonamides on neutrophil
myeloperoxidase-mediated iodination and cytotoxicity were studied using in vitro assays to measure these parameters. Leukocyte iodination was documented using a quantitative assay to measure the iodination of
protein by human neutrophils undergoing phagocytosis. Cytotoxicity for the tumor cell line LSTRA by human neutrophils activated by exposure to
phorbol myristate acetate was measured by a 51Cr release assay.
Dapsone,
diasone, and
sulfapyridine, at concentrations comparable to serum levels obtained by therapeutic doses of
drug, effectively inhibited iodination and cytotoxicity mediated by human neutrophils. Other
sulfonamides showed little inhibition of either iodination or cytotoxicity. The amount of inhibition was comparable to that seen with the inhibitors
azide or
cyanide and occurred in a dose dependent manner with all three drugs. A cell-free cytotoxic system using
myeloperoxidase,
iodide, a H2O2 generating system, and target cells also showed inhibition by
dapsone,
diasone and
sulfapyridine in a similar fashion. The active drugs inhibited both the intra- and the extracellular myeloperoxidase-H2O2-halide cytotoxic systems. Serial iodination studies of four
dermatitis herpetiformis patients, evaluated while taking
dapsone or
sulfapyridine, showed inhibition of iodination by either
drug. Levels of
IgA immune complexes, as measured by the Raji cell radioimmune assay adapted for
IgA, did not change when medication was withheld. These studies demonstrate that
dapsone,
diasone, and
sulfapyridine inhibit both neutrophil iodination and cytotoxicity for
tumor cells, while other
sulfonamides have no effect. This confirms previous studies showing inhibition by
myeloperoxidase mediated iodination by
dapsone. Furthermore, the effect on neutrophils is quickly reversible; in vivo administered
drug has no effect on in vitro function. The active drugs inhibit both intra- and extracellular cytotoxic systems. This may represent an important mechanism by which these drugs produce their
therapeutic effects when used to treat inflammatory
skin diseases.