Pretreatment with interleukin-33 reduces warm hepatic ischemia/ reperfusion injury in mice

Background Interleukin （IL）-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion （I/R） injury. Methods Male BALB/c mice （（22＋3） g） were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups： control group （laparotomy only, without blocking blood supply） and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups： control, model （injection of rabbit IgG polyclonal antibody）, recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, IL-4, IL-5, IL-13, interferon-y （IFN-y） and tumor necrosis factor-a （TNF-a） levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia （P 〉0.05） but increased significantly during reperfusion （P 〈0.05）. After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased （P 〈0.05）, and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls （P 〈0.05）. There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.

Follicular helper T lymphocytes in health and disease

A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall focus on the regulation of their development and function in health and disease. T FH can be characterized on the basis of their phenotype and the pattern of secretion of cytokines. This fact is useful to study their participation in the generation of antibody deficiency in primary immunodeficiency diseases such as common variable immunodeficiency, X-linked hyper Ig M syndrome orX-linked lymphoproliferative disease. Increased numbers of T FH have been demonstrated in several autoimmune diseases and are thought to play a role in the development of autoantibodies. In chronic viral infections caused by the human immunodeficiency virus, hepatitis B or C virus, increased circulating T FH have been observed, but their role in the protective immune response to these agents is under discussion. Likewise, an important role of T FH in the control of some experimental protozoan infections has been proposed, and it will be important to assess their relevance in order to design effective vaccination strategies.

Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.