Response of normal human keratinocytes to sulfur mustard: Cytokine release

Cytokines play a major role in both acute and chronic inflammatory processe s, including those produced by sulfur mustard (2,2 ' -dichlorodiethyl sulfi de, HD), This study describes responses of normal human epidermal keratinoc ytes (NHEK) to HD, defined by interleukin-1 beta (IL-1 beta), IL-6, IL-8 an d tumor necrosis factor alpha (TNF-alpha) release. Commercially available e nzyme-linked immunosorbent assay (ELISA) kits were used to measure the cyto kine release in NHEK during exposure to 100 and 300 muM of HD, Exposure to 100 muM Ho increased the release of cytokines, The amounts of IL-8 and TNF- alpha present in cell suspensions increased up to 59-fold and 4-fold, respe ctively, above control levels when NHEK were exposed to 300 muM HD Exposure of NHEK to 300 muM HD had a highly variable effect on the release of IL-1 beta, where sometimes the secretion of IL-1 beta increased above baseline l evel and at other times it decreased in cell suspensions. Supernatants were collected from cell culture flasks 24 h after exposure of 100 and 300 muM HD and significantly increased levels of IL-6 were observed. Interleukin-6 was released in a concentration-dependent manner, 3.6-fold up to 8.4-fold, respectively, in supernatant, These pro-inflammatory mediators IL-1 beta, I L-8, TNF-alpha and IL-6 may play an important role in Ho injury, The presen t findings suggest that the cytokine changes detected could be used as pote ntial biomarkers of cutaneous vesicant injury. Published in 2000 by John Wi ley & Sons, Ltd.