Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Immunol Cell Biol. 2012 Jul;90(6):611-9. doi: 10.1038/icb.2011.79. Epub 2011 Sep 27.
Hepatitis B virus infection is still a major global health problem, despite decades of research. Interleukin (IL)-22 induces acute phase reactants and chemokines, favors anti-microbial defence and protects tissues from damage. IL-22 is important in chronic skin inflammation, but its role in chronic hepatitis B (CHB) is unclear. This study explores the association between intra-hepatic IL-22 expression, its relevant associated cytokines and the severity of liver inflammation/fibrosis in CHB patients. IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines (CXCL-9, CXCL-10, CXCL-11), fibroblast growth factors and Kupffer cell (KC) numbers were measured in patients with CHB (n=65), acute hepatitis B (AHB; n=4), chronic hepatitis C (CHC; n=14) and non-viral hepatitis (n=23), using immunohistochemistry. Expression of IL-22, IL-17, IL-10, IL-6, non-ELR-CXC chemokines and number of KCs in liver tissues were substantially higher in AHB patients than others. In CHB patients, the expression of IL-22, IL-6, CXCL-9 and CXCL-10 were significantly higher with alanine aminotransferase (ALT) levels ≤ twice the upper limit of normal (ULN), compared with those with ALT levels >twice the ULN, whereas IL-10 and IL-17 showed a reverse pattern. IL-22 was inversely (P<0.01), but IL-17 was positively (P<0.05), correlated with the histological activity index) in these patients, and a significant negative correlation between the fibrosis stage and IL-22 or non-ELR-CXC chemokines was observed. Furthermore, immunofluorescent labeling demonstrated a close spatial association of IL-22, CXCL-9, -10 or -11 in the CHB liver. We speculate that IL-22 and non-ELR-CXC chemokines synergistically may provide protection in liver inflammation/fibrosis during CHB infection.
乙型肝炎病毒感染尽管经过了几十年的研究，仍然是一个主要的全球健康问题。白细胞介素（IL）-22 诱导急性期反应物和趋化因子，有利于抗微生物防御并保护组织免受损伤。IL-22 在慢性皮肤炎症中很重要，但在慢性乙型肝炎（CHB）中的作用尚不清楚。本研究探讨了 CHB 患者肝内 IL-22 表达及其相关细胞因子与肝炎症/纤维化严重程度之间的关系。使用免疫组织化学法测量了 CHB（n=65）、急性乙型肝炎（AHB；n=4）、慢性丙型肝炎（CHC；n=14）和非病毒性肝炎（n=23）患者的 IL-22、IL-17、IL-10、IL-6、非 ELR-CXC 趋化因子（CXCL-9、CXCL-10、CXCL-11）、成纤维细胞生长因子和库普弗细胞（KC）数量。与其他患者相比，AHB 患者肝组织中 IL-22、IL-17、IL-10、IL-6、非 ELR-CXC 趋化因子和 KC 数量的表达明显更高。在 CHB 患者中，与丙氨酸氨基转移酶（ALT）水平≤正常上限（ULN）的两倍相比，IL-22、IL-6、CXCL-9 和 CXCL-10 的表达水平显着更高，而 IL-10 和 IL-17 则表现出相反的模式。IL-22 与组织学活动指数呈负相关（P<0.01），但与组织学活动指数呈正相关（P<0.05），而 IL-22 或非 ELR-CXC 趋化因子与纤维化阶段呈显著负相关。此外，免疫荧光标记显示在 CHB 肝脏中 IL-22、CXCL-9、-10 或-11 之间存在密切的空间关联。我们推测，IL-22 和非 ELR-CXC 趋化因子可能协同提供 CHB 感染期间肝炎症/纤维化的保护作用。
