Kinetics of serum soluble tumour necrosis factor receptor (TNF-R) type-I and type-II after a single interferon-alpha (IFN-alpha) injection in chronic hepatitis C.
Circulating soluble TNF receptors, which act as TNF inhibitors, increase following the administration of IFN-alpha. Whether this is due to a direct IFN action or to indirect mechanisms involving the release of other cytokines is unclear. The kinetics of serum IFN, TNF, IL-6, IL-10, soluble TNF receptor type-I (sTNF-RI) and sTNF-RII were evaluated by enzyme immunoassays in 11 patients with chronic hepatitis C, following the first dose of recombinant human IFN-alpha2b (3 MU given subcutaneously). sTNF-RI concentrations paralleled IFN concentrations, rising from a mean +/- s.e.m. value of 3.5 +/- 0.3 ng/ml at baseline to a peak value of 5.5 +/- 0.5 ng/ml after 9 h, followed by a return to 4.1 +/- 0.4 ng/ml after 24 h (P = 0.0001). sTNF-RII concentrations, which were 7.6 +/- 0.5 ng/ml at baseline, fell initially to 6.9 +/- 0.5 ng/ml, to reach a peak at 24 h of 9.0 +/- 0.7 ng/ml (P < 0.0001). In contrast, the concentrations of TNF, IL-6 and IL-10 fluctuated with no significant changes at any time point. The area under the curve (AUC) of incremental IFN values had a strong positive correlation with the AUC of incremental sTNF-RI values (r = 0.75, P < 0.01). In patients with hepatitis C, IFN concentrations reached after a single dose of IFN were paralleled by correlationally increased concentrations of sTNF-RI, which are a much better marker of administered IFN than sTNF-RII, IL-6 or IL-10.
Fabris
C
C
Dipartimento di Patologia e Medicina Sperimentale e Clinica (DPMSC), University of Udine, Italy.
Del Forno
M
M
Falleti
E
E
Toniutto
P
P
Pirisi
M
M
D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D012995:Solubility
D015703:Antigens, CD; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D016753:Interleukin-10; D007372:Interferons