Analysis of the effect of IL-12 therapy on immunoregulatory T-cell subsets in patients with chronic hepatitis C infection.
OBJECTIVE
Aim of this study was to investigate the influence of IL-12 therapy on the production of immunoregulatory type 1/type 2-cytokines by peripheral blood mononuclear cells from patients with chronic hepatitis C.


METHODS
Peripheral blood mononuclear cells were isolated from 12 patients with chronic HCV infection before and after eight weeks of IL-12 application (0.03-0.5 micrograms/kg body weight). Peripheral blood mononuclear cells from 40 healthy blood donors served as a control group. The peripheral blood mononuclear cells were incubated for seven days with antigens stimulating specifically type 1 (tuberculin purified protein derivative) or type 2 T-cells (tetanus-toxoid). Furthermore, BCG (bacille Calmette-Guérin) was added to the cultures known to activate macrophages/antigen-presenting cells. Supernatants of peripheral blood mononuclear cells were analyzed for tuberculin purified protein derivative-induced production of the type 1 cytokine IFN-gamma, tetanus-toxoid-induced production of the type 2 cytokine IL-5 and the BCG-induced production of TNF-alpha by a double sandwich ELISA.


RESULTS
IL-12 therapy hardly influenced the regulatory type 1/type 2 T-cell reactivity. In contrast, BCG induced secretion of TNF-alpha was significantly higher after eight weeks of IL-12 therapy (4348 +/- 3083 pg/mL) than before treatment (1559 +/- 988 pgmL, p < 0.01). Clinically, serum alanine transaminase levels significantly decreased during IL-12 treatment but HCV-RNA persisted in all patients.


CONCLUSIONS
IL-12 therapy in patients with HCV does not alter the production of regulatory cytokines produced by type 1/type 2 TH cells. The significantly enhanced production of BCG-induced TNF-alpha may, however, indicate an activation of antigen presenting cells or natural killer cells.
Barth
Heidi
H
Medizinische Klinik, Innere Medizin II, Eberhard-Karls-Universität, Tübingen, Germany.
Klein
Reinhild
R
Berg
Peter A
PA
Wiedenmann
Bertram
B
Hopf
Uwe
U
Berg
Thomas
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000328:Adult; D016207:Cytokines / Q000032:analysis* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D016207:Cytokines; D018664:Interleukin-12