INDUCTION OF CIRCULATING IL-1 RECEPTOR ANTAGONIST BY IFN TREATMENT

This study was undertaken to determine whether IFN induce IL-1 recepto r antagonist (IL-1 Ra), a specific inhibitor of IL-1. Plasma samples w ere obtained from healthy volunteers (n = 5) and patients with chronic hepatitis C (n = 5) treated with IFN-alpha, and from patients with re nal cell carcinoma (n = 6) treated with IFN-gamma and assayed for IL-1 Ra by a specific radioimmunoassay. Both types of IFN were administere d subcutaneously. In vitro studies were carried out with PBMC from hea lthy volunteers. A single, low and nontoxic dose (1 X 10(6) U) of IFN- alpha induced circulating IL-1 Ra, which reached peak levels within 12 h. This effect was dose-dependent and more pronounced with a higher d ose (5 X 10(6) U). Peak IL-1 Ra levels 12 h after 5 X 10(6) U IFN-alph a were 4.16 +/- 0.35 ng/ml in healthy volunteers and 5.7 +/- 0.73 ng/m l in patients with chronic hepatitis C (difference not significant). T hereafter levels declined but remained elevated for 24 h. IFN-gamma tr eatment led only to a modest increase of circulating IL-1 Ra even at a dose of 400 mug; this dose, however, was associated with side effects similar to those seen after injection of 5 X 10(6) U IFN-alpha. PBMC stimulated with IFN-alpha or IFN-gamma produced IL-1 Ra in vitro. The induction of IL-1 Ra may contribute to the antiviral, anti-inflammator y, and antiproliferative effects of IFN.