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 inflammationand damage during late pregnancy and throughout lactation thanin pre- or early pregnancy or post lactation. This window ofsensitivity coincides with a period of elevated levels of pituitaryderivedprolactin or placental lactogen. In this study, we investigatedthe hypothesis that prolactin exerts an enhancing effect onozone-induced pulmonary inflammation and damage, thus presentinga plausible explanation for the sensitivity profile observedin rats. Hyperprolactinemia was achieved by using rats withsubcutaneous tumors that were derived from the MMQ tumor modelpreviously 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 MMQtumor, the MMQ_r tumor, which appeared spontaneously from a singlepassage of MMQ tumor tissue, produced elevated levels of corticosteronein addition to high levels of prolactin. These two subcutaneoustumors had markedly different effects on adrenal, thymus, andspleen weights because of the different hormonal milieu theygenerated. There was also a significant difference between MMQ-and MMQ_r-bearing rats in their inflammatory response to acuteozone exposure as assessed by polymorphonuclear leukocytes (PMNs)in the airways. Rats with MMQ tumors were not significantlydifferent from non-tumor-bearing controls in their baselinelevel of airway PMNs and PMN inflammation following ozone exposure,whereas MMQ_r-bearing rats had significantly elevated baselinePMNs in their airways and a greater PMN response to inhaledozone. The hormonal milieu and elevated PMNs in the airwaysof both unexposed and ozone-exposed rats with MMQ_r tumors weresimilar to levels observed in lactating rats. The role of corticosteronein pulmonary inflammation in this model was investigated furtherby treating MMQ tumor-bearing rats with dexamethasone. Dexamethasonewas effective in producing changes in organ weights similarto those observed in MMQ_r rats, but did not elicit higher airwayPMN concentrations in unexposed rats as observed in the MMQ_rrats. We conclude that in this animal model prolactin did notsignificantly elevate airway PMN inflammation induced by ozone,and supplementation with exogenous glucocorticoid did not duplicatethe endogenous airway PMNs numbers observed in MMQ_r-bearingrats or lactating rats.