MODULATION OF THE INFLAMMATORY EFFECTS OF INHALED OZONE IN RATS BY SUBCUTANEOUS PROLACTIN-SECRETING, PITUITARY-DERIVED TUMORS

Rats are more sensitive to ozone-induced pulmonary inflammation and da mage during late pregnancy and throughout lactation than in pre- or ea rly pregnancy or postlactation. This window of sensitivity coincides w ith a period of elevated levels of pituitary-derived prolactin or plac ental lactogen. In this study, we investigated the hypothesis that pro lactin exerts an enhancing effect on ozone-induced pulmonary inflammat ion and damage, thus presenting a plausible explanation for the sensit ivity profile observed in rats. Hyperprolactinemia was achieved by usi ng rats with subcutaneous tumors that were derived from the MMQ tumor model previously described by Adler and co-workers (Adler, R. A., Krie g, R. J., Farrell, M. E., Deiss, W. P., and MacLeod, R. M., Metabolism 40, 286-291, 1991). A variant of the MMQ tumor, the MMQ(r) tumor, whi ch appeared spontaneously from a single passage of MMQ tumor tissue, p roduced elevated levels of corticosterone in addition to high levels o f prolactin. These two subcutaneous tumors had markedly different effe cts on adrenal, thymus, and spleen weights because of the different ho rmonal milieu they generated. There was also a significant difference between MMQ- and MMQ(r)-bearing rats in their inflammatory response to acute ozone exposure as assessed by polymorphonuclear leukocytes (PMN s) in the airways. Rats with MMQ tumors were not significantly differe nt from non-tumor-bearing controls in their baseline level of airway P MNs and PMN inflammation following ozone exposure, whereas MMQ(r)-bear ing rats had significantly elevated baseline PMNs in their airways and a greater PMN response to inhaled ozone. The hormonal milieu and elev ated PMNs in the airways of both unexposed and ozone-exposed rats with MMQ(r) tumors were similar to levels observed In lactating rats. The role of corticosterone in pulmonary inflammation in this model was inv estigated further by treating MMQ tumor-bearing rats with dexamethason e. Dexamethasone was effective in producing changes in organ weights s imilar to those observed in MMQ(r) rats, but did not elicit higher air way PMN concentrations in unexposed rats as observed in the MMQ(r) rat s. We conclude that in this animal model prolactin did not significant ly elevate airway PMN inflammation induced by ozone, and supplementati on with exogenous glucocorticoid did not duplicate the endogenous airw ay PMNs numbers observed in MMQ(r)-bearing rats or lactating rats. (C) 1997 Society of Toxicology.