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


CONCLUSIONS
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.
Yamamoto
T
T
Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.
Sawada
Y
Y
Katayama
I
I
Nishioka
K
K
D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma