IMMUNOPATHOGEN. OF OCCUP. DIS. DUE TO REACT. CHEMICALS

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Work related exposure to reactive chemicals can result in occupational lung disease that may involve immunologic and nonimmunologic mechanisms. Isocyanates are reactive chemicals that are known to induce bronchial sensitization and occupational asthma. Mechanisms underlying diisocyanate induced asthma have not yet been fully defined. Only a minority of such cases have been associated with IgE responses to diisocyanate human serum albumin (HSA) conjugates. The pathogenetic significance of IgG responses to these antigens which have ben observed have not been elucidated. Data from our laboratory have demonstrated in vitro production of a cytokine, leukocyte inhibitory factor (LIF), produced in response to diisocyanate protein conjugates in patients with occupational asthma. Exposure to chromic acid resulting in late onset anaphylactoid reaction has been described among electroplating workers. Although preliminary studies have failed to demonstrate specific IgE mechanisms, in vitro demonstration of LIF has been measured in affected workers. Thus it appears that cell mediated immunity may play a significant role in the pathogenesis of occupational diseases caused by reactive chemicals. The objective of this study is to define the role of cell mediated immunity in the pathogenesis of clinical disease induced by diisocyanates and chromic acid. The study population will be divided into 3 groups of workers: 20 workers with exposure to diphenylmethane diisocyanate (MDI); 5 workers with chromate induced anaphylactoid reactions; and 10 nonexposed control subjects. HSA conjugates of MDI, TDI, HDI and potassium dichromate will be prepared and chemically characterized. Sera from these groups will be studied for possible specific IgG, IgG4 and IgE humoral responses to the relevant chemical hapten-HSA antigens. In vivo evaluation will be performed by performing immediate epicutaneous testing and delayed patch testing to relevant conjugates. Assays for LIF in response to relevant conjugate antigens will be determined in all subjects. Lymphocytes will be further isolated and antigen-specific blast transformation studies will be performed with relevant antigens. Supernatants obtained from lymphocytes preincubated with chromate or diisocyanate conjugates will be assayed for the presence of histamine releasing factors (HRF).