ORGANOPHOSPHATE INSECTICIDES AND ACQUIRED IMMUNITY

点击翻译按钮获取中文摘要

Previous studies have demonstrated that organophosphate treatments which produced severe, prolonged cholinergic stress also suppressed the primary Ig response to sheep red blood cells (SRBC) in mice. Organophosphate treatments which did not produce similar stress were not immunosuppressive. This suggested that the observed immunosuppression might be a consequence of the glucocorticoid elevation which one would anticipate as a result of the toxic chemical stress. Additional observations suggest that the immunosuppression may not be completely dependent upon the stress. Thus, for most organophosphates tested, there was an apparent selectivity with respect to decreases in Ig producing cells as compared to total spleen cell population. In fact, EPN decreased the Ig response without causing any suppression of spleen cellularity. The specific aims are directed at determining the relative contributions of stress-dependent and stress-independent actions of organophosphates to the observed immunosuppression. The time-course of plasma corticosterone levels after organophosphates will be determined and correlated with immunosuppression. The effects of organophosphates upon the Ig response will be compared in control and adrenalectomized mice. The Mishell-Dutton assay will be employed to identify the spleen cell populations which are responsible for the observed immunosuppression. Additional studies are included to further characterize the effects of organophosphates upon the secondary anti-SRBC response. In other studies, we have demonstrated that repeated organophosphate treatments, which did not cause cholinergic crisis, enhanced the rate of clearance of L. monocytogenes from livers and spleens of infected mice. Additional studies are directed at the mechanism of this apparent enhancement of resistance to bacterial infection. In other studies, macrophage-like cells grown in culture inactivated paraoxon under conditions which suggest involvement of cell esterases. Since esterases are involved in several immune functions, we will determine the effect of insecticides upon macrophage function. In all studies where appropriate, esterases will be monitored as an index of organophosphate exposure and/or toxicity and in an attempt to correlate esterase inhibition with altered immune function.