The Studies Of Effects Of Interleukin 13 (IL-13) On Pulmonary Fibrosis And Related Intervening Mechanisms

At present, the pathogenesis of end - stage, chronic lung disease is thought to be characterized by an initial inflammation response following by fibroprolifer-ation and deposition of extracellular matrix. Many of these chronic lung disorders share a variety of common properties, including an unknown etiology, undefined mechanism of initiation and maintenance, and progressive fibrosis. It is estimated in the foreign data that idiopathic pulmonary fibrosis (IFF) are to be up to 30 per 100 000, and the median survival time after biopsy - confirmed IFF is 3 years. Less than 30 percent of patients with IFF have reaction to traditional treatment. All these reflect the limit scientific and mechanistic understanding of these disorders. However recent studies have shown that cytokine networks are likely operative in dictation the progression of these diseases, as these mediators can influence fibroblasts activation, proliferation and collagen deposition during the maintenance of chronic fibrotic lung disease. Recent studies suggest that type 2 T helper lymphocytes ( Th2 cells) and their products play critical roles in the pathogenesis of pulmonary fibrosis. When the balance between Thl and Th2 cytokines shifts to Th2, the pulmonary fibrosis happens. Therefore, the balancing doctrines give us a new way to explore the mechanisms of pulmonary fibrosis.IL - 13 is a pleiotropic cytokine produced in large quantities by activated CD4+ Th2 lymphocytes. IL - 13 is often described as anti - inflammatory mediator because it can inhibit Thl - dominated cell - mediated immune response. A few data demonstrate IL - 13 is the dominant Th2 cytokines regulating fibrosis. IL - 13 stimulated collagen production in fibrosis. IL - 13 inhibitors may be of general therapeutic benefit in preventing damaging tissue fibrosis resulting from Th2 - dominated inflammatory response. Bleomycin model is common used toexplore mechanisms involved in the pathogenesis of pulmonary fibrosis, which resembles in human with idiopathic interstitial pneumonia (IIP). The lately study shows that bleomycin induced a Th2 - dominated inflammatory response.Therefore, We explore the role of IL -13 on pulmonary fibrosis in patients with IFF and bleomycin - induced Wister rats and the effects of recombinant IL -13 on proliferation rate and expression of type I collagen in fibroblasts.1. Interleukin -13 (IL -13) expression in lung tissues of blomycin -induced ratsObjective; To investigate the potential role of IL - 13 during the process of acute pulmonary injury and fibrosis with a rat model of bleomycin ?induced pulmonary fibroisis. To try to elucidate that macrophage is the dominant cell to secret IL -13, and IL - 13 probably induce tissue fibrosis by selectively stimulating and activating transforming growth factor(31 ( TGFpl). Methods: Wister rats were instilled single dose of bleomycin (5mg/kg in 0. 2ml -0. 3ml saline) via trachea. Control rats received only sterile saline. Rats were divided into 5 groups of 10 rats each, with each group further subdivided equally between control and experimental or bleomycin - treated groups. Rats were killed at days 1, 3,7, 14and 28 after bleomycin or saline endotracheal. At each time point, the right lungs were lavaged with saline at 37 C , then differential cell counts were performed and hydroxyproline(HYP) in right lung tissues was determined. Im-munohistochemistry assay for IL - 13, TGF|31 were performed in the cells in bronchial alveolar lavage fluid(BALF). Left lung, fixed in 4% paraformalde-hyde buffer, were used for in situ hybridation analysis for IL - 13 mRNA. The results were analyzed by image analysis system. Results: (1) In BLM group, total cells in BALF were increased at dayl, peaked at days 3, and returned to the normal level at days 28. Alveolar macrophages in BALF fell to the peak point at days 3, whereas the percentages of neutrophils, as well as lymphocytes were increased to the peak at days 3. (2) HE staining showed that BLM groups at days 7 stimulate a great deal of inflammatory cells infiltr...