Dapsone hydroxylamine inhibits the LTB₄-induced chemotaxis of polymorphonuclear leukocytes into human skin: Results of a pilot study

Abstract.

Objective: Dapsone (4,4'diaminodiphenylsulfone) is effective in treating leprosy, chronic inflammatory conditions and opportunistic infections in HIV patients. By the oral route, the sulfone is metabolized to monoacetyldapsone (MADDS) and dapsone hydroxylamine (DDS-NOH). We have addressed the question as to whether these dapsone metabolites have anti-inflammatory properties of their own in vivo.¶Treatment and Methods: After two weeks topical pre-treatment with MADDS (1%), DDS-NOH (1%) and clobetasol proprionate (CP; 0.05%) dissolved in acetone, as a reference, 10 ng leukotriene B₄ (LTB₄) were applied on the upper arms of eight healthy volunteers. After 24 h, biopsies were taken and the polymorphonuclear leukocytes (PMN) were quantified fluorometrically using elastase as marker enzyme.¶Results: MADDS did not show any inhibitory activity on trafficking of PMN compared to the corresponding control and nontreated area (untreated: 790 ± 450 PMN/10 μg skin; p > 0.05, acetone: 840 > 578 PMN/10 μg skin; MADDS: 1099 > 556 PMN/10 μg skin), whereas DDS-NOH caused a statistically significant inhibition of PMN accumulation as did the reference CP (DDS-NOH: 128 > 143 PMN/10 μg skin; CP: 86 > 131 PMN/10 μg skin, p < 0.01).¶Conclusions: These results indicate that DDS-NOH has anti-inflammatory potential which might contribute to the effectiveness of dapsone therapy.