17 -Estradiol Antiinflammatory Activity in Carrageenan-Induced Pleurisy

Abstract

We have recently demonstrated that 17beta-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 carrageneen-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.

Gender Differences in Murine Airway Responsiveness and Lipopolysaccharide-Induced Inflammation

“…Considerable experimental and clinical data indicate that female sex hormones may influence lung function, airway responsiveness, and inflammation (4,5,8,18); however, their effects appear to vary depending on the experimental system used and the end points analyzed. Indeed, whereas estradiol has been shown to reduce airway responsiveness in rats (18), equivocal effects of estrogens have been reported in animal models of lung injury and include antiinflammatory (3,5), proinflammatory (4), and profibrotic (6) outcomes. Conversely, much less is known regarding the influence of male sex hormones on lung function and disease.…”

“…Whereas the role of androgens has not been addressed in detail, estrogens appear to equivocally influence lung injury outcomes depending on the model (3)(4)(5)(6). Bacterial LPS, a ubiquitous airborne contaminant and recognized exacerbating factor for the development and severity of asthma (7), causes airway inflammation and hyperresponsiveness in humans and animals.…”

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…Divergent effects of estrogens have been reported for T cell activation [48] as compared with microglia and astroglia based on different hormone concentrations ( [60,82]). Additionally, expression of iNOS is reduced in certain cell types, including microglia ( [26,49,203,241,261]) while hormone actually increases the expression of endothelial and neuronal subtypes of NOS ( [191,203]). Thus, it is important to fully characterize the signal transduction mechanisms of estrogen signaling in different cell types of the CNS and the relative contributions of each of the two isoforms of estrogen receptor involved, so that appropriate therapeutic agents can be devised.…”

Effects of estrogen receptor agonists on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats

“…Estrogen has been shown to affect inflammatory mediators such as cytokines in a number of systems and has been shown to decrease inflammation in experimental models of anterior uveitis (Miyamoto et al, 1999), carrageenan-induced pleurisy in the lungs (Cuzzocrea et al, 2001;Cuzzocrea et al, 2000) and adjuvant-induced arthritis (Badger et al, 1999). On the other hand, estrogen promotes prostatitis (Naslund et al, 1988), stimulates edema (Tchernitchin and Galand, 1983) and increases vascular permeability and influx of macrophages in the uterus (De and Wood, 1990;Kaushic et al, 1998).…”