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17ß-Estradiol Antiinflammatory Activity in Carrageenan-Induced Pleurisy

Institute of Pharmacology (S.C., G.C., I.S., A.P.C.), University of Messina, Italy; Institute of Pharmacology Sciences (S.S., A.M.), University of Milano, Italy; Department of Experimental Pharmacology (L.S.), University "Federico II", Naples, Italy; Department of Biomorphology (E.M.), School of Medicine, University of Messina, Italy

Address all correspondence and requests for reprints to: Salvatore Cuzzocrea, Ph.D., Institute of Pharmacology, School of Medicine, University of Messina, Piazza XX Settembre no. 4, 98123 Messina, Italy. E-mail: salvator{at}www.unime.it

We have recently demonstrated that 17ß-estradiol (E₂) opposes cytokine-dependent increase of inducible nitric oxide synthase (iNOS) activity in rat smooth muscle cells and proposed that this effect might be associated to an antiinflammatory activity of this hormone. In the present study, we examine the E₂ effects on a well-known in vivo model of inflammation. We show that, in carrageenan treatment of ovariectomized rats, prior exposure to E₂ significantly attenuated inflammatory response as measured by histological examination and exudate production. The effect was visible with a single injection of a physiological dose of E₂ 1 h before the carrageenan treatment and was blocked by coadministration of the estrogen receptor antagonists ICI 182,780 or tamoxifen. This latter observation suggests that the effect is receptor mediated. The mechanisms by which estradiol has beneficial effects in this model of inflammation are unclear: we show that in hormonally treated rats there is a decrease in polymorphonuclear cells migration as shown by cell counting and myeloperoxidase measurement. In addition, E₂ pretreatment opposes carrrageneen- induced high lipid peroxidation maintaining malondialdehyde activity at control levels. E₂ treatment decreases NO production and the activity of iNOS with consequent diminished nitrite synthesis and nitrosine accumulation. Finally, immunohistochemical analysis for poly (ADP-ribose) synthase revealed a positive staining in lungs from carrageenan-treated rats that was blocked by estradiol treatment. We conclude that E₂ attenuates the degree of inflammation and tissue damage associated with carrageenan-induced pleurisy in the rat.

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