title: Relationship between interferon-gamma, interleukin-10, and interleukin-12 production in chronic hepatitis C and in vitro effects of interferon-alpha.
abstract: In the current study, increased interferon (IFN)-gamma, interleukin (IL)-10, and IL-12 p40 serum levels were observed in patients with chronic hepatitis C (CHC) compared to controls. Patients also displayed an increased spontaneous IFN-gamma release but a deficient peripheral blood mononuclear cells (PBMC) IFN-gamma production following stimulation with Staphylococcus aureus Cowan I strain (SAC). No difference was found with reference to spontaneous or phytohaemagglutinin (PHA)-induced IL-10 release between patients and controls, whereas a higher IL-12 p70 and IL-12 p40 secretion triggered by SAC was observed in patients. Moreover, IL-12 p40/p70 ratio following SAC stimulation was higher in patients compared to controls and a negative correlation was found between this ratio and IFN-gamma amounts. Recombinant IL-12 (rIL-12) as well as neutralizing anti-IL-10 monoclonal antibodies (mAbs) were able to restore the compromised IFN-gamma production. Of note, anti-IL-10 supplementation induced a lower IL-12 p40/p70 ratio in HCV subjects as compared to controls. Finally, IFN-alpha upregulated in vitro IFN-gamma, IL-10, and IL-12 p70 release but not IL-12 p40 secretion, this giving rise to a normalization of IL-12 p40/p70 ratio. The data suggest the occurrence of an enhanced responsiveness to IL-10 modulating effects, likely mediated by an imbalance of IL-12 p40/p70 ratio, in chronic HCV infection. Cytokine balance restoration might thus contribute to achieve therapeutical results in chronic hepatitis C.
authors.affiliation: Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari Medical School, Italy. g.piazzolla@intmed.uniba.it
authors.forename: G
authors.initials: G
authors.lastname: Piazzolla
authors.forename: C
authors.initials: C
authors.lastname: Tortorella
authors.forename: O
authors.initials: O
authors.lastname: Schiraldi
authors.forename: S
authors.initials: S
authors.lastname: Antonaci
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D018123:Receptors, Interleukin; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma