title: IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Xiang
authors.forename: Honglian
authors.initials: H
authors.lastname: Gui
authors.forename: Nicholas J C
authors.initials: NJ
authors.lastname: King
authors.forename: Louise
authors.initials: L
authors.lastname: Cole
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Shisan
authors.initials: S
authors.lastname: Bao
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D054357:Chemokine CXCL10 / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007728:Kupffer Cells; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008103:Liver Cirrhosis / Q000276:immunology; D008297:Male; D000097043:Interleukin-22
chemical_list: D000410:Alanine Transaminase; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D005346:Fibroblast Growth Factors; D016753:Interleukin-10; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D000097043:Interleukin-22; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human