INTERFERON-ALPHA INDUCES CIRCULATING TUMOR-NECROSIS-FACTOR RECEPTOR P55 IN HUMANS

In the present studies we investigated the effect of interferon-alpha (IFN alpha) on the release of the soluble (extracellular) form of the tumor necrosis factor p55 receptor (TNFsRp55), because TNFsRp55 is a n atural antagonist of tumor necrosis factor (TNF)-induced inflammation and also might be part of the antiinflammatory properties of IFN alpha . Plasma levels of TNFsRp55 were measured by a specific radioimmunoass ay in five healthy volunteers and in five patients with chronic hepati tis C treated with IFN alpha. Levels showed a significant increase aft er a single injection of 5.0 million U IFN alpha in both healthy and h epatitis patient groups. Peak values (3.5 to 4.5 ng/mL) were observed within 12 hours of beginning treatment. Thereafter, levels promptly de clined, reaching baseline values within 24 hours, TNF alpha and C-reac tive protein (CRP) levels were below the detection limit in the same p lasma samples. In addition, IFN alpha suppressed significantly interle ukin (IL)-1 alpha-induced TNF alpha protein synthesis by human periphe ral blood mononuclear cells. These results suggest that the antiinflam matory properties of IFN alpha may be, in part, also due to the induct ion and/or release of TNF soluble receptors and the suppression of TNF alpha synthesis. (C) 1995 by The American Society of Hematology.