Modulation of Cytokines in TNBS Induced Colitis Treated with Estrogen

Abstract

Background: Epidemiological studies showed that pregnant women and women under birth-control pills experienced less inflammation than other women. Even if estrogens were thought to have more pro- than anti-inflammatory-like reaction (because of their inflammatory-like reaction on the ovarian follicle maturation) there are now numerous experimental models where the lack of estrogens facilitates the onset of inflammation Objectives: This study investigated the anti-inflammatory effect of estrogen in TNBS induced colitis models, focusing specifically on the morphological changes, the activity of mast cells and the expression of cytokines (Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α)), extra cellular matrix (fibronectin and collagen IV) as well as reactive oxidative species (ROS). Materials and Methods: 120 adult male SpragueDawley rats (n=120), weighing 250 to 300g, were divided into 4 groups: Group I: induced with colitis, not receiving treatment, Group II induced with colitis and treated with estrogen (17β-estradiol), Group III receiving estrogen only, Group IV not provided with anything. In groups I and II colitis was induced according to previously established procedures: 2,4,6-Trinitrobenzenesulfonic acid solution (TNBS) (n=20 for each group) and Dextran Sulfate Sodium Salt (DSS) (n=20 for each group). Rats were observed daily where scores was given to signs and symptoms. Biopsies of the colon, jejunum, liver and kidney were extracted from the rats on days 7, 14, 28 and 56, where macroscopic, microscopic and molecular evaluations were performed. Results: The rats from Group II receiving estrogen treatment, expressed statistically reduced clinical scores by approximately 10%. The gross morphologic inflammation alterations showed statistically significant amelioration when the rats were treated with estrogen by about 20 %. Estrogen reduced significantly the expression of collagen IV and fibronectin protein expressions as well as IL-6, TNF-α, and fibronectin gene expression by 20 %. ROS expression tested with the dihydroethidine (DHE) staining was significantly decreased by 30 %. Conclusions: Estrogen in experimental colitis depicted an overall preventive and or protective role. Rats treated with estrogen showed less inflammation at all time points, less necrosis and less production of ROS compared to non-estrogen treated animals.