Abstract:The regulatory effects of the active form of vitamin D, 1-a, 25-dihydroxyvitamin D 3 (1-a, 25 (OH) 2 D 3 ) were assessed on the cytokine and chemokine secretion induced by sulfur mustard on human skin fibroblasts and human epidermal keratinocytes. Stimulation of human skin fibroblasts with sulfur mustard (10 ª4 M for 24 hr at 37ae) resulted in approximately a 5 times increase in the secretion of interleukin-6 and over a 10 times increase for interleukin-8, which was inhibited by 1-a, 25 (OH) 2 D 3 , at AE10 ª9 M. 1-a, 25 (OH) 2 D 3 also suppressed interleukin-8 secretion by 5 times and interleukin-6 by 4 times on sulfur mustard-stimulated human epidermal keratinocytes at concentrations AE 10 ª9 M. The effect of 1-a, 25 (OH) 2 D 3 was dose-dependent for the suppression of interleukin-6 and interleukin-8 induced by sulfur mustard on human skin fibroblasts/human epidermal keratinocytes, apparent at nanomolar concentrations. Our results indicate that the suppression of these inflammatory mediators by 1-a, 25 (OH) 2 D 3 is dependent on the source of the primary cultures, cell densities, and kinetics of pretreatments. In contrast to the inhibition of cytokine/chemokine production, cell proliferation was enhanced by almost 1.7 times on treated human epidermal keratinocytes with 1-a, 25 (OH) 2 D 3 (1¿10 ª9 M) after sulfur mustard-stimulation (10 ª4 M for 24 hr at 37aeC). The observed enhancement diversified based on cell density, and kinetics of pretreatment with a maximal synergism (s) observed at 1¿10 ª9 M. Photomicrographs show typical signs of cellular degeneration caused by sulfur mustard such as chromatin condensation. The observed cellular degeneration was lessened when human epidermal keratinocytes were treated with 1-a, 25 (OH) 2 D 3 (2¿10 ª9 M). 1-a, 25(OH) 2 D 3 could be an alternative treatment for cutaneous inflammation disorders caused by sulfur mustard because we have demonstrated its ability to suppress inflammatory mediators and enhanced cell proliferation in human skin cells stimulated with sulfur mustard.In an attempt to develop antidotes with specific activity, low toxicity and few side effects for treatment of dermatological disorders caused by sulfur mustard, we investigated the effect of 1-a, 25-dihydroxyvitamin D 3 (1-a, 25 (OH) 2 D 3 ) on cytokine/chemokine production and cell proliferation in two different human skin cell types, human skin fibroblasts and human epidermal keratinocytes. Mustard received its name from its smell (onion, garlic, mustard) (Medema 1986). When mustard was first used by the Germans, the Allies called it Hun Stoffe (German stuff). When distilled, or near pure, it is known as sulfur mustard.Skin injuries caused by sulfur mustard are a complex phenomenon that involve resident epidermal cells, fibroblasts of dermis, and endothelial cells as well as invading leukocytes interacting with each other under the control of