Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophagecells

Objective. To investigate nitric oxide (NO) production and inducible NO syn thase expression by cultured peripheral blood mononuclear cells (PBMC) in p atients with systemic sclerosis (SSc). Methods. Eighteen patients with SSc were compared with two control groups: 16 patients with rheumatoid arthritis (RA) and 23 patients with mechanical sciatica. Nitrate was determined by fluorimetry in plasma and by spectropho tometry in supernatants. Inducible NO synthase (iNOS) was detected in cultu red PBMC by immunofluorescence, immunoblotting and flow cytometry With or w ithout treatment of the cells with interleukin (IL) 1 beta + tumour necrosi s factor alpha (TNF-alpha), IL-4 or interferon gamma (IFN-gamma) from day 1 to day 5. Results. NO metabolite concentrations were lower in SSc patients (mean +/- S.E.M.. 34.3 +/- 2.63 mu mol/l) than in RA (48.3 +/- 2.82 mu mol/l; P < 0.0 2) and sciatica (43.3 +/- 5.24 <mu>mol/l; P < 0.03.) patients. iNOS was det ected in cultured monocytes in all three groups but induction occurred on d ay 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the Stimul us. Conclusions. The concentrations of NO metabolites are decreased in SSc pati ents and the metabolism of these compounds in PBMC is altered. Low levels o f NO, a vasodilator, may be involved in vasospasm, which is critical in SSc . This may have therapeutic implications.