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

Abstract

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.

Fig. 1

Kinetics of IFN-α, soluble TNF-RI and soluble TNF-RII serum concentrations, following administration of recombinant human IFN-α2b (3 MU subcutaneously; arrow). *Significant value (< 0.05 level) by Bonferroni multiple comparisons by trial factor time, in comparison with baseline. Error bars represent s.e.m.

Fig. 2

Kinetics of IL-6, IL-10 and TNF serum concentrations, following administration of recombinant human IFN-α2b (3 MU subcutaneously; arrow). *Significant value (< 0.05 level) by Bonferroni multiple comparisons by trial factor time, in comparison with baseline. Error bars represent s.e.m.

Fig. 3

Correlation between the values of area under the curve (AUC) of increments of serum IFN-α and soluble TNF-RI.