© 1997 Oxford University Press
research-article |
Modulation of the Inflammatory Effects of Inhaled Ozone in Rats by Subcutaneous Prolactin-Secreting, Pituitary-Derived Tumors1
*Nelson Institute of Environmental Medicine, New York University Medical Center 550 First Ave., New York, New York 10016
Department of Internal Medicine, Medical College of Virginia/Virginia Commonwealth University, and Endocrinology and Metabolism Section, Hunter Holmes McGuire Veterans Affairs Medical Center 1201 Broad Rock Boulevard, Richmond, Virginia 23249
Received October 8, 1996; accepted March 4, 1997
Rats are more sensitive to ozone-induced pulmonary inflammation and damage during late pregnancy and throughout lactation than in pre- or early pregnancy or post lactation. This window of sensitivity coincides with a period of elevated levels of pituitaryderived prolactin or placental lactogen. In this study, we investigated the hypothesis that prolactin exerts an enhancing effect on ozone-induced pulmonary inflammation and damage, thus presenting a plausible explanation for the sensitivity profile observed in rats. Hyperprolactinemia was achieved by using rats with subcutaneous tumors that were derived from the MMQ tumor model previously described by Adler and co-workers (Adler, R. A., Krieg, R. J., Farrell, M. E., Deiss, W. P., and MacLeod, R. M., Metabolism 40, 286–291, 1991). A variant of the MMQ tumor, the MMQr tumor, which appeared spontaneously from a single passage of MMQ tumor tissue, produced elevated levels of corticosterone in addition to high levels of prolactin. These two subcutaneous tumors had markedly different effects on adrenal, thymus, and spleen weights because of the different hormonal milieu they generated. There was also a significant difference between MMQ- and MMQr-bearing rats in their inflammatory response to acute ozone exposure as assessed by polymorphonuclear leukocytes (PMNs) in the airways. Rats with MMQ tumors were not significantly different from non-tumor-bearing controls in their baseline level of airway PMNs and PMN inflammation following ozone exposure, whereas MMQr-bearing rats had significantly elevated baseline PMNs in their airways and a greater PMN response to inhaled ozone. The hormonal milieu and elevated PMNs in the airways of both unexposed and ozone-exposed rats with MMQr tumors were similar to levels observed in lactating rats. The role of corticosterone in pulmonary inflammation in this model was investigated further by treating MMQ tumor-bearing rats with dexamethasone. Dexamethasone was effective in producing changes in organ weights similar to those observed in MMQr rats, but did not elicit higher airway PMN concentrations in unexposed rats as observed in the MMQr rats. We conclude that in this animal model prolactin did not significantly elevate airway PMN inflammation induced by ozone, and supplementation with exogenous glucocorticoid did not duplicate the endogenous airway PMNs numbers observed in MMQr-bearing rats or lactating rats.