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The British Journal of Rheumatology, Vol 37, 1123-1125, Copyright © 1998 by British Society for Rheumatology

ORIGINAL PAPERS

Increased production of nitric oxide stimulated by interleukin-1beta in peripheral blood mononuclear cells in patients with systemic sclerosis

T Yamamoto, Y Sawada, I Katayama and K Nishioka
Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.

OBJECTIVE: Nitric oxide (NO) is an important mediator of immune and inflammatory responses, and has recently been suggested to play some role in the pathogenesis of autoimmune disorders. In this study, we have examined whether peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produce higher levels of NO spontaneously or in response to several stimulations in vitro. METHODS: PBMC were obtained from 14 patients with SSc and 15 normal volunteers. Release of NO after stimulation with lipopolysaccharide (LPS), interleukin-lbeta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) was determined by Griess reagents. RESULTS: PBMC from SSc patients exhibited a higher level of spontaneous release of NO (13.4+/-3.8 microM) than those from control subjects (8.9+/-1.6 microM), but without significance. Incubation of PBMC for 24 h with stimulants caused an increase in NO production both in normal subjects and SSc patients. Stimulation with 10 U/ml IL-1beta induced a significantly increased NO production in SSc patients (22.1+/-6.6 microM) compared with normal subjects (12.3+/-4. microM) (P < 0.05); however, in contrast, incubation with other stimulants showed no significant differences in NO production between SSc patients and normal subjects. CONCLUSION: These results suggest the abnormal regulation of NO production in PBMC of scleroderma patients in response to IL-1beta, which might contribute, in part, to the fibrotic process in SSc.
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