title: Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-alpha) receptors in type C chronic liver disease.
abstract: We previously reported that the number of TNF-alpha-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-alphaRI (p55) and -alphaRII (p75), and IL-10, all of which act as TNF-alpha buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-alphaR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-alphaRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-alphaRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.
authors.affiliation: First Department of Internal Medicine, Aichi Medical University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kakumu
authors.forename: A
authors.initials: A
authors.lastname: Okumura
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: A
authors.initials: A
authors.lastname: Enomoto
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshika
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D019409:Interleukin-15 / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000276:immunology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D019409:Interleukin-15; D012367:RNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D007372:Interferons; D000637:Transaminases