Dapsone inhibits local production of toxic reactive oxygen species, myeloperoxidase, and elastase, but this seems unlikely as a principal mode of action because the clinical response to dapsone is characterized by decreasing the neutrophil numbers.) Other investigators have shown that dapsone may impair neutrophil chemotaxis by interfering with activation of adhesion molecule CD11b/CD18 in vitro. However, this seems to require a higher concentration of dapsone than therapeutic levels measured in vivo. The concentration of dapsone we used in the present study is within the ranges required for therapeutic serum levels of 0.5 to 5 mg/mL. We found that the lower concentration of dapsone of 0.3 mg/mL inhibited LPS-induced IL-8 secretion, and this effect was not due to cell toxicity as measured by the number of viable cells.
Effect of dapsone
Schmidt reported that dapsone, in a therapeutic concentration, inhibited the bullous pemphigoid IgG-mediated IL-8 release from cultured normal human epidermal keratinocytes and that dapsone did not depress basal IL-8 level. These data are similar to the present results using NHBE cells. It also has been reported that dapsone decreases production of tumor necrosis factor a and IL-8 in peripheral blood mononuclear cells following LPS stimulation.
Effect of dapsone on LPS-induced NF-kB p65 phosphorylation. Growth factors were withdrawn from the culture medium 24 h before LPS or dapsone exposure. The threonine phosphorylation of NF-kB p65 was measured by Western blotting. The band intensity was calculated with National Institutes of Health Image J software. A, LPS 10 mg/mL significantly phosphorylated NF-kB p65 up to 2 h, and this was inhibited by dapsone 1 mg/mL. B, Dapsone inhibited LPS-induced NF-kB p65 phosphorylation, and this was dose dependent. Data are presented as mean ± SE from more than three independent experiments. *P < .05. **P<.01 compared with control subjects (LPS —, dapsone —, at each time). #P < .05. ##P < . 01 compared with LPS alone. NF-kB = nuclear factor-kB. See Figure 2 legend for expansion of other abbreviation.