Studies of IL28B genotype in the setting of liver transplantation in HCV infection have shown that both donor and recipient IL28B genotypes have a significant effect on treatment outcomes.52 Although it is tempting to imagine a simple, tissue-specific mechanism for the IL28B effect on treatment response, these results collectively suggest an influence of IL28B genotype from both hepatic and extrahepatic tissues. Among the agents in development for treatment of HCV

is the pegylated formulation of human IFN-λ1, which has shown antiviral activity both in cellular models and in vivo and is currently in phase II clinical trials.21-23 Given the influence of host genetic variation in the IFN-λ pathway on treatment response, recombinant IFN-λ products represent Torin 1 price a promising avenue in the future of HCV therapeutics and may also provide valuable information regarding the mechanism of the IL28B genetic effect. “
“Autoimmune www.selleckchem.com/products/3-methyladenine.html hepatitis (AIH), like many

autoimmune diseases, is most prevalent in young women. The immunological basis of this age and sex susceptibility bias was investigated in a murine model of AIH. Xenoimmunization of 7-week-old female C57BL/6 mice resulted in more severe AIH with higher levels of liver inflammation, serum alanine aminotransferase, specific T-cell cytotoxicity, and autoantibody than younger and older females. Vaccinated males developed selleck kinase inhibitor minimal liver inflammation and higher percentages of CD4+CD25+FoxP3+ regulatory T cell in peripheral blood mononuclear cells, spleen, and liver than females. Regulatory T cells (Tregs) were virtually absent in liver-lymphocytes infiltrates of females. Castration of C57BL/6 mice, with or without 17β-estradiol supplementation, did not modify susceptibility in males, nor Treg numbers, suggesting minimal contribution of testosterone and estradiol to autoimmune hepatitis

(AIH) susceptibility. Xenoimmunized Aire(+/0) mouse displayed similar AIH susceptibility, sex bias, and Tregs numbers as C57BL/6 mice, suggesting that susceptibility in females is not the result of less stringent thymic central tolerance. Autoreactive B cell response against formiminotransferase-cyclodeaminase correlated with disease activity, possibly linking B-cell autoreactivity and AIH pathogenesis. Conclusion: Peripheral tolerance and development of regulatory T cells after self-mimicking antigen exposure, and not sexual hormone nor central tolerance, are the main factors for susceptibility to AIH in females. HEPATOLOGY 2010 Prevalence of most autoimmune diseases shows a striking sex difference, with women being affected more often than men.1, 2 The ratio of female patients to male ranges from 20:1 in Sjögren’s syndrome, to 3:2 in multiple sclerosis.2 Less frequently, the ratio approaches 1:1, as in ulcerative colitis and diabetes.