title: Effect of IL-12 on T-cell immune responses in patients with chronic HCV infection.
abstract: As the host's immune responses may determine the outcome of hepatitis C virus (HCV) infection, and interleukin (IL)-12 plays an essential role in host defense against infectious diseases, we studied the antigen-specific and non-specific cellular immune responses in patients with chronic HCV infection. A proliferative response to phytohemagglutinin (PHA) was found in all 20 patients. Of the 20, 8 (40%) displayed a lymphocyte proliferation in response to HCV antigen c22, 2 (10%) to c33, 6 (30%) to c100-3, and 1 (5%) to NS5. The addition of rhIL-12 to cultures of peripheral blood mononuclear cells (PBMC) stimulated with PHA significantly enhanced the proliferative responses in normal controls as well as in HCV-infected subjects. The increased proliferation was also observed in HCV-infected patients when PBMC were co-cultured with HCV antigens c22 and c100-3 in the presence of rhIL-12. The production of interferon gamma (IFNgamma), IL-2, IL-4 and IL-10 was observed in 7 (58.3%), 5 (41.7%), 3 (25.0%) and 5 (41.7%) HCV-infected individuals stimulated with c22, and in 4 (33.3%), 2 (16.7%), 2 (16.7%) and 2 (16.7%) with c100-3, respectively. All HCV-infected individuals had increased production of cytokines IFNgamma, IL-2, IL-4 and IL-10 in supernatants of PBMC after stimulation with PHA. IL-12 significantly augmented Th1 cytokine production in HCV-infected individuals stimulated with PHA and with HCV antigens. In conclusion, deficient cellular immune responses are present in HCV-infected patients and IL-12 can enhance the immune responses in these patients.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Hunan Medical University, Changsha, PR China. xgfan@hotmail.com
authors.forename: X G
authors.initials: XG
authors.lastname: Fan
authors.forename: F Q
authors.initials: FQ
authors.lastname: Tang
authors.forename: H
authors.initials: H
authors.lastname: Yi
authors.forename: W E
authors.initials: WE
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Houghton
authors.forename: G L
authors.initials: GL
authors.lastname: Hu
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D018936:Hepatitis C Antigens; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D016207:Cytokines; D018936:Hepatitis C Antigens; D018664:Interleukin-12; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C499352:core protein p22, Hepatitis C virus; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase