The protective role of endogenous estrogens in carrageenan-induced lung injury in the rat

Background: We have recently demonstrated that 17 beta -estradiol (E2) inhi bits the increase of inducible nitric oxide synthetase (MOS) activity in se lected model systems such as macrophages, microglia, smooth muscle cells, a nd proposed that this effect might be associated with an antiinflammatory a ctivity of this hormone. Here we investigate the effects of endogenous estr ogens in rats subjected to carrageenan-induced pleurisy. Materials and Methods: Adult female rats were ovariectomized 3 weeks before the experiments to deplete circulating estrogens. Selected inflammatory ma rkers, landmarks of the delayed phase of carrageenan-induced pleurisy, were measured in intact (N-OVX), and ovariectomized (OVX) female rats. In addit ion, the effect of hormone replacement was evaluated in ovariectomized rats with intraperitoneal injection of 17 beta -estradiol (E2; 50 mug/kg) 1 hr before carrageenan treatment (OVX + E2). Results: Ovariectomy enhanced the carrageenan- induced degree of pleural ex udation and polymorphonuclear leukocyte migration in rats subjected to carr ageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and lipid per oxidation were significantly increased in estrogens-deprived rats. The iNOS in lung samples was significantly increased by the surgery. The increase o f MOS activity was correlated with a marked enhancement in the production o f TNF-alpha and IL-1 beta. Immunohistochemical analysis for P-selectin and ICAM-1, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) re vealed a positive staining in lungs from carrageenan-treated rats, which wa s markedly enhanced in ovariectomized rats when compared to cycling rats, p articularly in the estrous phase of the cycle. Estrogen replacement counter acted the effect of surgery on all of the above indicators of lung inflamma tion, suggesting that in the cycling rat this hormone plays a key role in t he increased sensitivity to inflammatory injury observed in the OVX rat. Conclusion: This study demonstrates that endogenous estrogens production pl ays an important protective role against carrageenan-induced acute inflamma tion by decreasing the expression of specific markers of the delayed phase of this well-known model of acute inflammation.