Impacto deletério da interleucina- 9 na fisiologia hepatorenal

Abstract

IL-9 is a pleiotropic cytokine, recently recognized as belonging to Th9 cells that are involved in various pathologies. We aimed to evaluate the role of IL-9 in the course of hepatic and renal fibrosis. Female C57BL/6 mice were treated subcutaneously with IL-9 100ng and 200ng during 40 days, alternating every 5 days each application, the negative control of which was treated with PBS and positive control with CCL4. IL-9 demonstrated fibrogenic activity, leading to increased collagen I and III deposition in both liver and kidney, as well as triggering lobular hepatitis with stage 1 fibrosis. In addition, IL-9 induced an inflammatory response with recruitment of lymphocytes, neutrophils, and macrophages In both organs. The inflammation was present in the region of the portal and parenchymal zone in the liver, and in the cortical and medullary zone in the kidneys. IL-9 regulated the gene expression of TGF-β and α-SMA, being responsible for the activation of Ito cells and renal myofibroblasts. The proinflammatory activity of IL-9 triggered oxidative stress, leading to oxidation of proteins and lipids present in the cell membrane of hepatocytes and renal cells. At the same time, there was a decrease in the activity of antioxidant enzymes as well as the total antioxidant capacity of the liver and kidney. Our results suggest deleterious role of IL-9 in the increase of renal and hepatic fibrosis, with exacerbation of the inflammatory response, indicating that it may be a therapeutic target for the treatment of these diseases.