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Rheumatology 2001; 40: 1089-1096
© 2001 British Society for Rheumatology
Original Papers |
Low levels of nitric oxide (NO) in systemic sclerosis: inducible NO synthase production is decreased in cultured peripheral blood monocyte/macrophage cells
Departments of Rheumatology A,
1 Biochemistry A and
2 Pharmacology, Cochin Hospital, René Descartes University, Paris 75014, France
Objective. To investigate nitric oxide (NO) production and inducible NO synthase expression by cultured peripheral blood mononuclear cells (PBMC) in patients 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 spectrophotometry in supernatants. Inducible NO synthase (iNOS) was detected in cultured PBMC by immunofluorescence, immunoblotting and flow cytometry with or without treatment of the cells with interleukin (IL) 1ß+ tumour necrosis factor 
(TNF-), IL-4 or interferon 
(IFN-) from day 1 to day 5.
Results. NO metabolite concentrations were lower in SSc patients (mean±s.e.m. 34.3±2.63 µmol/l) than in RA (48.3±2.82 µmol/l; P<0.02) and sciatica (43.3±5.24 µmol/l; P<0.03) patients. iNOS was detected in cultured monocytes in all three groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus.
Conclusions. The concentrations of NO metabolites are decreased in SSc patients and the metabolism of these compounds in PBMC is altered. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may have therapeutic implications.
KEY WORDS: Nitric oxide, Mononuclear cells, Systemic sclerosis.
Correspondence to: A. Kahan, Rhumatologie A, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.
* These authors contributed equally to the work.
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