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SUPPRESSION OF ALLERGIC IMMUNE RESPONSES TO HOUSE DUST MITE (HDM) IN RATS EXPOSED TO 2,3,7,8-TCDD
Citation:
Luebke, R W., C. Copeland, M. Daniels, M. Lambert, AND M I. Gilmour. SUPPRESSION OF ALLERGIC IMMUNE RESPONSES TO HOUSE DUST MITE (HDM) IN RATS EXPOSED TO 2,3,7,8-TCDD. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 62(1):71-79, (2001).
Description:
Abstract
Exposure to various xenobiotics, including oxidant gases, diesel exhaust and certain pesticides, has been reported to exacerbate pulmonary allergic hypersensitivity responses. Increased lymphocyte proliferative responses to parasite antigens or increased antibody responses to sheep erythrocyte have also been reported in rats exposed to TCDD before infection or immunization. As a result, these studies were conducted to test the hypothesis that TCDD exposure exacerbates the allergic response to house dust mite antigen. Brown Norway rats were injected i.p. with 0, 1, 10 or 30 g TCDD/kg 7 days before intratracheal (i.t.) sensitization to semipurified house dust mite allergen (HDM). Fourteen days later, rats were challenged with HDM and immediate bronchospasm was measured. At this time point, plus 2 and 7 days later, inflammatory cells in bronchoalveolar lavage fluid (BALF), HDM-specific IgE levels in serum and BALF, and HDM-driven cell proliferation in bronchial lymph nodes and spleen were evaluated. TCDD exposure decreased both immediate bronchoconstriction and specific IgE synthesis after HDM challenge; 7 days later, HDM-specific IgE responses remained suppressed, while total IgE levels were increased in rats exposed to the highest dose of TCDD. HDM challenge alone significantly increased cellular and biochemical indicators of lung injury, all of which were suppressed by TCDD exposure. The proliferative response of lymph node cells, but not of spleen cells, to HDM was also suppressed at the highest TCDD dose, although the splenic response to Con A was elevated. It appears that early events in the response to HDM are affected by TCDD exposure, since message for IL5 was dramatically reduced 2 days after sensitization, but not after challenge. We therefore conclude that TCDD exposure suppressed, rather than enhanced, the development of allergic immune responses and the expression of immune-mediated lung disease.
Key words: dioxin, dust mite, allergy, immunosuppression, IgE, lung, rats