Vitamin D Deficiency: Correlation to Interleukin-17 in Chronic Hepatitis C Virus Egyptian Patients

Abstract

Summary T he epidemiology and burden of HCV infection varies throughout the world, with country-specific prevalence ranging from <1% to >10%.Egypt has the highest prevalence of hepatitis C in the world depending on the populations covered; overall estimates of the HCV rate in the general population have range between 10 and 20%. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. Human IL-17 (IL-17) - producing CD4Tcells, Th 17, comprise a proinflammatory T-cell subset.Several key cytokines, including IL-1, IL-6, tumor necrosis factor alpha, and IL-23 create a cytokinemilieu that regulates the differentiation and expansion of human TH17 cell. IL-17A can mobilize, recruit, and activate neutrophils, leading to massive tissue inflammation, and promote the progression of autoimmune disease. Furthermore, serumIL-17 levels are increased and serve as a marker of the severity of acute hepatic injury. Vitamin D is a fat-soluble vitamin which is essential for maintenance of bone mineralization through the regulation of calcium and phosphorus homeostasis. Vitamin D also exhibits many non-skeletal effects. Acting through the VDR, 1,25-dihydroxyvitamin D is a potent immune system modulator. The VDR is expressed by most cells of the immune system, including regulatory T cells and antigen-presenting cells. There is considerable scientific evidence that 1,25-dihydroxyvitamin D has a variety of effects on immune system function, which may enhance innate immunity and inhibit the development of autoimmunity. Conversely, vitamin D deficiency may compromise the integrity of the immune system and lead to inappropriate immune responses. Vitamin D undergoes hepatic 25-hydroxylation, rendering the liver critical to the metabolic activation of this vitamin. Vitamin D deficiency is highly prevalent in CLD patients, and vitamin D levels are inversely related to the severity of CLD. Declining levels of carrier proteins such as albumin and vitamin D-binding protein might also be critical in CLD. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has a direct repressive effect on the expression of IL-17A in T cells.The mechanism of 1,25(OH)2D3 repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). The present study was aiming to evaluate the serum concentration of Vit D and IL-17 in patients with chronic hepatitis C liver disease, and also to assess if there is a correlation between them. Two groups of individuals were included in this study. Patients group, comprising 30 Egyptian chronic(HCV)-infected patients and control group that included age- and sex-matched 20healthy volunteers. Quantitative assays of serum Vit D and IL-17, using commercially supplied ELISA were performed for both groups. A statistically high significant difference was observed as regard serum levels of Vit D and IL-17 between the studied groups; patients group had lower levels of Vit D and higher levels of IL-17. There is no correlation between vitamin D and IL-17 neither among patients group nor control group.