CYTOKINE PRODUCTION IN SCLERODERMA PATIENTS - EFFECTS OF THERAPY WITHEITHER ILOPROST OR NIFEDIPINE

Objective. To compare the long-term effects of intermittent infusion o f iloprost with those of oral nifedipine on the in vitro production of cytokines in patients with systemic sclerosis (SSc), and to evaluate their relationship with the effects of the two treatments on clinical parameters. Methods. The production of cytokines by alloactivated circ ulating mononucleated cells was assessed before and after one year of treatment in a subset of 31 patients enrolled in a 12-month randomized clinical trial. Nineteen patients were treated with a 5-day (8 hr per day), 2.0 ng/kg per minute infusion followed by a I-day infusion ever y 6 weeks; 12 patients were treated with an oral slow-release formulat ion of nifedipine, 20 mg twice daily. quantitative determinations of i nterleukin-1 beta(IL1-beta) and interleukin-6 (IL6) in the culture sup ernatants were performed with a commercial ELISA; the levels of tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma(IFN-gamma) wer e measured by specific radioimmunometric assays. Results. The producti on of IL1-beta was significantly lower in the iloprost group than in t he nifedipine group. Both the cutaneous fibrosis and the capillaroscop ic patterns were better in patients treated with iloprost than in pati ents treated with nifedipine. There was a significant positive covaria nce between IL1-beta changes and the changes in both the skin score an d the capillaroscopic score. Conclusion. There are several mechanisms by which iloprost could exert its clinical efficacy. Vasodilatation an d inhibition of platelet aggregation are certainly important, but they are transient. We suggest that the long-lasting modulation of the cyt okine network observed in the present study could be another potential mechanism responsible for the persistent efficacy of iloprost despite its intermittent administration.