Inflammatory cytokines analysis in C57BL/6 mouse skin after dermal exposure with chemical threat agent phosgene oxime

Abstract

Phosgene Oxime (dichloroform oxime; CX), an urticant categorized as a vesicating agent, is a potential chemical threat agent. Its exposure causes rapid and painful dermal injury and systemic toxic effects. CX exposure can result in enzyme inactivation, corrosive injury, and cell death with rapid tissue destruction, and induce the recruitment of immune cells. However, the mechanism of CX‐induced skin toxicity and inflammation is not known. Studies in our lab have shown that CX exposure causes mast cell degranulation and release of inflammatory mediators like COX‐2, MMP‐9, myeloperoxidase, and an inflammatory response in the skin. In the present study, we analyzed the inflammatory cytokine profile in male and female C57BL/6 mouse skin following dermal CX exposure (neat CX for either 0.5 or 1.0 min using two 12 mm vapor caps on the dorsal skin at MRIGlobal). Cytokine array analyses showed an increase in the pro‐inflammatory cytokines IL‐6 (Interleukin 6) and TNF‐α (Tumor Necrosis Factor Alpha) in both male and female mice at 24h post CX‐exposure. KC (neutrophil chemoattractant), MCP‐1 (Monocyte chemoattractant), MCSF (Macrophage colony‐stimulating factor) and RANTES (T cell, monocyte attractant) increased in both sexes at day 3 post CX‐exposure, showing involvement of immune cells in the CX‐induced injury. IL‐13, an allergic inflammation and several diseases’ mediator was found to be increased at later time point in female mice and at 2 hours after 1.0 min CX exposure in male mice. IL‐4 and IL‐5 levels decreased at 24 h but were increased at day 3 post 0.5 min CX exposure. Altogether, our results show immune cell infiltration with changes in inflammatory cytokines. Similar Inflammatory cytokine changes from CX exposure were observed in male and female mice; however, slightly different patterns were evident in some cytokines in female mice that related to the observed difference in the inflammatory response and somewhat faster dermal wound healing. Further molecular analysis is underway to determine the signaling pathways involved in CX‐induced dermal inflammation and toxicity for identifying the therapeutic targets.