Cytokine production in scleroderma patients: effects of therapy with either iloprost or nifedipine.
OBJECTIVE
To compare the long-term effects of intermittent infusion of 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 circulating 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 1-day infusion every 6 weeks; 12 patients were treated with an oral slow-release formulation of nifedipine, 20 mg twice daily. Quantitative determinations of interleukin-1 beta (IL1-beta) and interleukin-6 (IL6) in the culture supernatants were performed with a commercial ELISA; the levels of tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured by specific radioimmunometric assays.


RESULTS
The production of IL1-beta was significantly lower in the iloprost group than in the nifedipine group. Both the cutaneous fibrosis and the capillaroscopic patterns were better in patients treated with iloprost than in patients treated with nifedipine. There was a significant positive covariance between IL1-beta changes and the changes in both the skin score and the capillaroscopic score.


CONCLUSIONS
There are several mechanisms by which iloprost could exert its clinical efficacy. Vasodilatation and inhibition of platelet aggregation are certainly important, but they are transient. We suggest that the long-lasting modulation of the cytokine network observed in the present study could be another potential mechanism responsible for the persistent efficacy of iloprost despite its intermittent administration.
Della Bella
S
S
Institute of Internal Medicine, Infectious Diseases and Immunopathology, IRCCS Ospedale Maggiore di Milano, Italy.
Molteni
M
M
Mascagni
B
B
Zulian
C
C
Compasso
S
S
Scorza
R
R
D000328:Adult; D002196:Capillaries / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D005260:Female; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009543:Nifedipine; D016285:Iloprost