Survivors of an acute, sub-lethal irritant gas exposure may present with persistent long-term respiratory symptoms and/or functional impairment. These symptoms may result from enhanced sensitivity to antigen. Inflammation is the hallmark of irritant gas injury and many of the superficial differences observed are related to the site of action, which is determined by physical/chemical properties of the irritant, rather than intrinsic differences in the response. Chlorine is widely used and frequently involved in industrial or transportation accidents, and has intermediate solubility; therefore, it may exert its primary effects of all portions of the respiratory tract. Since purposeful exposure of humans to high levels of chlorine could never be justified, in this proposal, long-term respiratory effects following chlorine exposure will be evaluated in an animal model. Fisher 344 rats will be exposed to chlorine gas, in dose-dependent fashion; this will ensure induction of a range of sub-lethal injuries. The effects of chlorine exposure on immune responsiveness, will be evaluated. Rats will be sensitized, by nose-only exposure, to aerosolized ovalbumin (OA), at various intervals (2 hr, 1, 7, 30, and 60 days) post-chlorine exposure. Following sensitization to OA, local and systemic antibody responses will be quantitated using an enzyme linked immunosorbent assay and passive cutaneous anaphylaxis testing. To evaluate cellular responsiveness, lymphocyte transformation, using cells isolated from the spleen and the lung associated lymph nodes, and cultured with OA or concanavalin A will be performed. The experiments outlined in this proposal are designed to examine the outcome of chlorine exposure, but the results will likely apply to other primary irritants by virtue of their common pathogenetic mechanisms, and/or respiratory tract and lung inflammation. If the findings indicate enhanced susceptibility to specific sensitization, this would provide guidance in the design of studies or surveillance programs for exposed working programs.
