Cytokine-Mediated Immunopathogenesis of Hepatitis B Virus Infections

Abstract

Hepatitis B virus (HBV) infection is a worldwide health problem, with approximately one third of populations have been infected, among which 3-5% of adults and more than 90% of children developed to chronic HBV infection. Host immune factors play essential roles in the outcome of HBV infection. Thus, ineffective immune response against HBV may result in persistent virus replications and liver necroinflammations, then lead to chronic HBV infection, liver cirrhosis, and even hepatocellular carcinoma. Cytokine balance was shown to be an important immune characteristic in the development and progression of hepatitis B, as well as in an effective antiviral immunity. Large numbers of cytokines are not only involved in the initiation and regulation of immune responses but also contributing directly or indirectly to the inhibition of virus replication. Besides, cytokines initiate downstream signaling pathway activities by binding to specific receptors expressed on the target cells and play important roles in the responses against viral infections and, therefore, might affect susceptibility to HBV and/or the natural course of the infection. Since cytokines are the primary causes of inflammation and mediates liver injury after HBV infection, we have discussed recent advances on the roles of various cytokines [including T helper type 1 cells (Th1), Th2, Th17, regulatory T cells (Treg)-related cytokines] in different phases of HBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection. We then focus on experimental therapeutic applications of cytokines to gain a better understanding of this newly emerging aspect of disease pathogenesis.

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

“…Host immune factors are essential in the immune-pathogenesis of HBV infection through genetic and epigenetic modifications [37,38] and via the effects of cytokines [39]. An ineffective immune response against HBV may result in persistent virus replication and liver inflammation, leading to CHB, LC and HCC [39].…”

“…An ineffective immune response against HBV may result in persistent virus replication and liver inflammation, leading to CHB, LC and HCC [39]. ISG15 appears to act as an immune-modulator regulating the expression of cytokines, in particular of the IFN signalling pathway.…”

Involvement of Interleukin 6 in Hepatitis B Viral Infection

“…These complications do not result from a direct cytopathic effect of the virus itself, but from the immune response of the host that affects both outcome and disease progression [2,3]. Cytokines have been shown to be engaged in regulating hepatocyte functions, and play a fundamental role in HBV infection immunopathogenesis [4]. Among these cytokines [5], increasing importance has been attached to the involvement of interleukin 6 (IL-6) in HBV infection.…”

Type 1 innate lymphoid cells contribute to the pathogenesis of chronic hepatitis B

“…TTG AAT GTC CA R TCG CTT CCC TGT TTT AGC TGC IL-13 F CCT CAT GGC GCT TTT GTT GAC R TCT GGT TCT GGG TGA TGT TGA IL-4 F GAC ATC TTT GCT GCC TCC A R TAC TCT GGT TGG CTT CCT TCA IL-12 F CCT TGC ACT TCT GAA GAG ATT GA R ACA GGG CCA TCA TAA AAG AGG T IL-33 F TGA CGG TGT TGA TGG TAA GAT G R ACA GAG TGT TCC TTG TTG TTG G GAPDH F CGG AGT CAACGG ATT TGG TCG TAT R AGC CTTCTC CAT GGTGGT GAA GAC F, forward; R, reverse. Helper ILCs from CHB patients produced more type I cytokines than type II cytokines As type I and type II cytokines are known to be involved in CHB pathogenesis, 19 and helper ILCs are known to function primarily through their secreted cytokines, 7,9,18 we investigated whether ILC1s and ILC2s contribute to the HBV-related alterations in type I and type II cytokine profiles. We found that the mRNA levels of IFN-g and IL-13 were enhanced in the FACS-isolated helper ILCs from CHB patients compared with healthy controls but that the mRNA level of IL-4 did not differ between the two groups.…”