TH1/TH2 serum cytokine profiles and soluble TNF-receptor response in patients with chronic hepatitis C during recombinant human interleukin-12 (rHuIL-12) treatment.
Interleukin-12 (IL-12) has many antiviral properties both in vitro and in vivo, such as enhancing cytotoxic lymphocyte reaction, promoting Th1-helper cell response and inducing interferon-gamma - (IFN-gamma) production. The present study investigated possible antiviral effects of recombinant human IL-12 in vivo in 11 chronic hepatitis patients treated with rHuIL-12 subcutaneously in 3 different dosages (0.03, 0.1, 0.5 microg/kg) once weekly for a period of 10 weeks. ELISA was employed to determine before onset of therapy the serum concentrations of IL-12, IL-12p40, IFN-gamma, IL-4, IL-10, tumor mecrosis factor-alpha (TNF-alpha), TNFR p55 and p75, as well as on days 3, 5, 8, 10, 12, 15, 17, 22 after onset of therapy and subsequently weekly until the end of the treatment period and at the end of the 12 months' postobservatory period. The HCV-RNS serum concentration was determined by means of an RT-PCR method. Two to three days after the subcutaneous rHuIL-12 injections there was a transient significant rise of n the serum concentrations of IL-12, IL-12p40, IFN-gamma and TNFR p55, followed by a decrease to the original level. The increases of the IL-12 and IFN-gamma serum concentrations were dose-dependent. In patients where there was a decline of the HCV-RNS concentration in the serum we confirmed a trend to higher IL-12 serum concentrations. The serum levels of IL-2, TNF-alpha and IL-10 fluctuated only during the treatment period. The present study showed that a once-a-week injection of rHuIL-12 results in a merely transient rise of the IL-12, IL-12-p40- and IFN-gamma serum concentrations. This may offer an explanation for the unsatisfactory clinical efficiency of the substance.
Medizinische Klinik II, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
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G
Teuber
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S
Rossol
J-H
JH
Lee
C F
CF
Dietrich
S
S
Zeuzem
D000328:Adult; D016207:Cytokines / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000187:drug effects*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome
D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D018664:Interleukin-12