Menkès C J, Allanore Y, Borderie D, Hilliquin P, Hernvann A, Ekindjian O, Kahan A
Service de Rhumatologie A, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques-75679 Paris.
Bull Acad Natl Med. 2001;185(3):509-22; discussion 522-3.
We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or 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 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications.
我们研究了系统性硬化症(SSc)患者外周血单个核细胞(PBMC)中一氧化氮(NO)的产生及诱导型一氧化氮合酶(iNOS)的表达。将18例SSc患者与两个对照组进行比较:16例类风湿关节炎患者(RA)和23例机械性坐骨神经痛患者。通过荧光法测定血清中亚硝酸盐和硝酸盐的总量,通过分光光度法测定上清液中亚硝酸盐和硝酸盐的总量。在第1天至第5天,使用或不使用白细胞介素-1β+肿瘤坏死因子-α、白细胞介素-4或干扰素-γ,通过免疫荧光、免疫印迹和流式细胞术检测培养的PBMC中诱导型iNOS。SSc患者血浆中NO代谢物浓度(34.3μmol/L±2.63标准误)低于RA患者(48.3μmol/L±2.2;p<0.02)和坐骨神经痛患者(43.3μmol/L±5.24;p<0.03)。在3组培养的单核细胞中均检测到iNOS,但无论刺激因素如何,RA组在第1天、坐骨神经痛组在第2天、SSc组仅在第3天出现诱导。SSc患者中NO代谢物浓度降低,PBMC中iNOS的诱导延迟。低水平的NO作为一种血管扩张剂,可能参与血管痉挛,而血管痉挛在SSc中至关重要。这可能提示了治疗意义。