Kinetics of serum soluble tumour necrosis factor receptor (TNF-R) type-I and type-II after a single interferon-alpha (IFN-alpha) injection in chronichepatitis C

Circulating soluble TNF receptors, which act as TNF inhibitors, increase fo llowing the administration of IFN-alpha. Whether this is clue to a direct I FN action or to indirect mechanisms involving-the release of other cytokine s is unclear. The kinetics of serum IFN, TNF, IL-6, IL-10, soluble TNF rece ptor type-I (sTNF-RI) and sTNF-RII were evaluated by enzyme immunoassays in 11 patients with chronic hepatitis C, following the first dose of recombin ant human IFN-alpha 2b (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, fo llowed by a return to 4.1 +/- 0.4 ng/ml after 24 h (P=0.0001). sTNF-RII con centrations, 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 in cremental IFN values had a strong positive correlation with the, AUC of inc remental sTNF-RI values (r = 0.75, P<0.01). In patients with hepatitis C, I FN concentrations reached after a single dose of IFN were paralleled by cor relationally increased concentrations of sTNF-RI, which are a much better m arker of administered IFN than sTNF-RII, IL-6 or IL-10.