Nitric oxide production and inducible nitric oxide synthase expression by monocytes in systemic sclerosis

We investigated nitric oxide (NO) production and inducible No synthase (iNO S) expression by cultured peripheral blood mononuclear cells (PBMC) in syst emic sclerosis (SSc). Eighteen patients with SSc were compared to two contr ol groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry i n sera and spectrophotometry in supernatants. Inducible iNOS was detected i n cultured PBMC by immunofluorescence, immunoblot and flow cytometry with o r without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mu mol/l +/ - 2.63 SEM) than in RA (48.3 mu mol/l +/- 2.2; p < 0.02) and sciatica (43.3 mu mol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monoc ytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciati ca and only on day 3 in SSc, whatever the stimulus. The concentrations of N O metabolites are decreased in SSc patients and the induction of iNOS in PB MC is delayed. Low levels of NO, a vasodilator, may be involved in vasospas m, which is critical in SSc. This may suggest therapeutic implications.