Specialized pro-resolving mediators as potential medical countermeasures in a pig model of chlorine gas-induced acute lung injury

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Chlorine is a highly utilized chemical in the U.S. with more than 10 million metric tons produced annually for purposes including water treatment, paper bleaching, and chemical manufacturing. Unfortunately, however, chlorine is also a toxic inhalant. Exposure to chlorine gas can cause immediate and sustained injury to the respiratory tract with the severity of injury depends on both concentration and duration of exposure. Whereas exposure to chlorine gas is typically accidental, it has been used as a chemical weapon since World War I. Despite its known chemical threat potencies since World War I, there is no specific antidote for chlorine gas-induced injuries. Recent studies in our laboratory revealed that post-exposure treatment with specialized pro-resolving mediators (SPMs), such as Resolvin D1 and Protectin D1 strongly improved lung injury outcomes in mice exposed to chlorine and hydrochloric acid (HCl). These SPMs are endogenous lipid derivatives produced during inflammation cascade that subsequently accelerates the resolution phase of inflammation. In the proposed grant application, we want to test these novel potential therapeutic agents in our well-established pig model of chlorine gas-induced acute lung injury following the FDA's animal rule.