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• W202915435 abstract "Traditional methods for toxicological assessment have implicated the immune system as an occasional target organ of toxic insult following chronic exposure to certain environmental chemicals or therapeutic drugs (xenobiotics). The immunotoxicity or immunomodulation induced can be expressed as autoimmunity, chemical hypersensitivity or immunosuppression. A flexible tiered approach for characterizing chemical- and drug-induced immunomodulation in laboratory animals has been developed and validated in several laboratories. This tiered approach has been used to characterize the immunomodulation induced by polycyclic aromatic hydrocarbons (PAH). Previous studies from this laboratory have demonstrated that subchronic exposure of B6C3F1 mice to PAH carcinogens, no non-carcinogenic congeners, suppresses both humoral and cell-mediated immunity (CMI) concurrently with decreased resistance to tumor, bacterial and viral challenge. In the studies reviewed here, the potent carcinogenic PAH 7, 12-dimethylbenz-[a]anthracene (DMBA) was subchronically administered subcutaneously at 5, 50, or 100 μg/g of body weight. Three to five days following final dosing, immune function and host resistance parameters were assessed. The antibody plaque-forming cell (PFC) response to T cell dependent and independent antigen challenge (sheep erythrocytes or TNP-LPS) was suppressed up to 97%. Suppression of antibody PFC responses correlated with a reduction of B cell progenitors (CFU-BL) in the spleen. Mitogen and alloantigen-induced (MLC) proliferation of splenocytes was suppressed up to 72%. Cytotoxic T cell (CTL) and natural killer cell (NK) tumor cytolysis of radiolabelled target cells were similarly depressed up to 93 and 55%, respectively. Impairment of CMI correlated with increased susceptibility to challenge with PYB6 sarcoma cells and Listeria monocytogenes.Because of indications that T-helper cell function was suppressed, splenocytes from DMBA-exposed mice were sensitized to alloantigens (MLC and CTL) in the presence of interleukin-2 (IL-2). CTL and MLC suppression could be completely restored by the addition of the T cell growth supporting lymphokine (IL-2) during the inductive phase of CTL generation, although suppression of the antibody PFC response was unaffected by addition of IL-2. The study presented suggests that immunomodulation induced by xenobiotics can occur at specific cell loci and can be detected and characterized by the flexible approach described." @default.
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• W202915435 date "1986-01-01" @default.
• W202915435 modified "2023-09-27" @default.
• W202915435 title "Modulation of Immunity by Xenobiotics" @default.
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• W202915435 doi "https://doi.org/10.1016/b978-0-08-032008-3.50033-3" @default.
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