Cytokines and HCV-related autoimmune disorders.
Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-γ-inducible CXC chemokine ligand (CXCL)9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases-mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes-are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-α may result in viral clearance during persistent infection and revert this process. Theoretically agents that selectively neutralize CXCL10 could increase patient responsiveness to traditional IFN-based HCV therapy. Several studies have reported IL-28B polymorphisms and circulating CXCL10 may be a prognostic markers for HCV treatment efficacy in HCV genotype 1 infection.
Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126, Pisa, Italy, alessandro.antonelli@med.unipi.it.
Alessandro
A
Antonelli
Silvia Martina
SM
Ferrari
Ilaria
I
Ruffilli
Poupak
P
Fallahi
D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D011379:Prognosis
D018925:Chemokines; D016207:Cytokines