Abstract
Dapsone (diaminodiphenylsulfone) has been used therapeutically for a variety of disorders in which mast cell participation has been demonstrated, including bullous pemphigoid and some form of necrotizing vasculitis. The mechanism of action of dapsone in these disorders is unknown but potentially relates to inhibition of mast cell activation and prevention of generation and/or release of mast cell mediators. Evidence for this possibility has been obtained in rat mast cells in which dapsone in a concentration-dependent manner prevented generation of prostaglandin D 2 PGD 2 from exogenous or endogenous arachidonic acid with 50% inhibition achieved at 1 and 0.2 to 0.4 mM, respectively. Dapsone inhibited cyclooxygenase conversion of arachidonic acid to PGD 2 but not the GSH-dependent conversion of 14C-PGH 2 to PGD 2 by PGH-D isomerase in broken cell preparations. Dapsone prevented the immunologic generation of PGD 2 from antigen-challenged rat mast cells but did not affect the release of histamine. Thus dapsone may exert some of its therapeutic effects by prevention of mast cell PGD 2 generation.
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