Expression Pattern of Serum Cytokines in Hepatitis B Virus Infected Patients with Persistently Normal Alanine Aminotransferase Levels

Abstract

PurposeAbout 60–80 % of chronic hepatitis B virus (HBV) carriers are characterized with persistently normal alanine transaminase (ALT). Differences of cytokine expression are associated with the prognosis of HBV infection. We investigated the expression pattern of 30 cytokines associated with anti-HBV immunity in patients with normal ALT.MethodsFour patient groups (immune tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B, and control; 10 subjects per group) were assigned. Thirty cytokines, including IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20, CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-β1, were measured using a human cytokine antibody array. Signal intensities were obtained by laser scanner. Protein-protein interactions were analyzed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins).ResultsSignificant differences of signal intensities were observed for IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29. The lowest intensity was in controls. Among three HBV infection groups, significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL-23p19, and IL-29. The highest intensity was in the inactive group. All cytokines with significant differences were involved JAK-STAT signaling that up-regulate FOXP3, SOCS3 and MX1.ConclusionDifferential expression of cytokines in JAK-STAT signaling is an important factor associated with prognosis of HBV infection. The elevation of γC cytokines, IL-12p70, IL-23p19, and IL-29 may promote spontaneous HBeAg seroconversion and HBV clearance.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-013-9931-0) contains supplementary material, which is available to authorized users.

Association of Gene Polymorphisms and Serum Levels of IL-18 with the Susceptibility to Infection with Hepatitis B Virus

“…This future plan will be built on these findings to establish the link of genomic information of inflammatory and antiinflammatory regulators with the differential anti-HBV immunity and provide important insights into prognostic markers for disease progression and evaluation of treatment and vaccine responses of local population. Additional studies with larger samples and detailed clinical data are warranted in various local ethnic populations to avoid the limited study population included herein [32][33][34][35][36].…”

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

“…IL-4 production in OBI cases (102.36 1.1 pg/ml) and HBV carriers (108.361.8 pg/ml) compared to SHRs (84.761.6 pg/ml) were significant, agreeing with previous studies that reported a relationship between IL-4 production and viral persistence in hepatitis B infection. 9 Serum levels of IL-6 were also increased in OBI cases (17.161.1 pg/ml) and HBV carriers (18.461.3 pg/ml) compared to SHRs (7.861.0 pg/ml) (P,0.05). Serum IL-6 levels have been reported to be elevated in individuals with chronic hepatitis B infection, cirrhosis and hepatocellular carcinoma, 10 and serum IL-6 levels were in agreement with this reported relationship between this cytokine and the progression of HBV infection.…”

Predictive model for inflammation grades of chronic hepatitis B: Large‐scale analysis of clinical parameters and gene expressions

“…Microarray is a well‐established and widely used technology, which can effectively provide an image of gene expressions . Researchers have only identified several gene profiles in relative small number of HBV‐infected patients, some of which have investigated gene expressions with single clinical parameter, eg ALT or HBV expression . There are few studies systematically combining clinical parameters, gene expressions and pathological inflammation levels to acquire a comprehensive view of chronic hepatitis B (CHB), not to mention in a large‐scale sample size.…”

“…4 Researchers have only identified several gene profiles in relative small number of HBV-infected patients, 5,6 some of which have investigated gene expressions with single clinical parameter, eg ALT or HBV expression. 7 There are few studies systematically combining clinical parameters, gene expressions and pathological inflammation levels to acquire a comprehensive view of chronic hepatitis B (CHB), not to mention in a large-scale sample size. Other researchers began to explore a liquid biopsy method to assess liver function based on single clinical parameter or in other liver disease (eg chronic hepatitis C).…”