新诊断的、未经治疗的类风湿性关节炎和狼疮患者中不同的单核细胞反应模式可能导致C反应蛋白水平存在差异。

Different monocyte reaction patterns in newly diagnosed, untreated rheumatoid arthritis and lupus patients probably confer disparate C-reactive protein levels.

作者信息

Liou L B

机构信息

Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-yuan County, Taiwan.

出版信息

Clin Exp Rheumatol. 2003 Jul-Aug;21(4):437-44.

DOI:

PMID:12942694

Abstract

OBJECTIVES

To investigate the different capacities of monocytes to produce cytokines in newly diagnosed, untreated patients with rheumatoid arthritis (RA) or systemic lupus and to examine the possible correlation among serum C-reactive protein (CRP), cytokines, swollen joint counts, and erythrocyte sedimentation rates (ESR) in untreated RA patients.

METHODS

Monocytes from untreated RA or lupus patients were cultured in vitro with lipopolysaccharide (LPS, as bacterial infection) or immune complexes (as endogenous immune deviation) and supernatants were collected for cytokine determination. Sera from RA patients were assayed for interleukin-6 (IL-6), IL-1 beta, IL-10, tumor necrosis factor-alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra). These cytokines were related to serum CRP, swollen joint counts, and ESR.

RESULTS

RA monocytes uniformly produced IL-6, IL-1 beta, TNF-alpha, or IL-10 in vitro. In contrast, lupus monocytes could be divided into two subsets: (i) monocytes which produce cytokines on LPS stimulation but not on challenging with immune complexes; and (ii) monocytes which, interestingly, generate cytokines on stimulation by immune complexes but not LPS. These cytokines in turn stimulate the liver to synthesize CRP differently in the SLE subsets and RA patients. Moreover, serum IL-1ra levels correlated significantly with serum IL-6, IL-1 beta, and TNF-alpha concentrations (p = 0.005, 0.008, or 0.040, respectively), but not with IL-10 (p = 0.582) in RA patients.

CONCLUSIONS

Two lupus subsets exist that react either to LPS or immune complexes to produce CRP-inducing cytokines, in contrast to homogeneous RA monocytes. This is the first report that different reaction patterns of CRP-inducing cytokine production in RA and lupus monocytes probably underlie the high CRP levels in RA versus low heterogeneity in lupus. The correlation of serum IL-1ra levels with serum IL-6, IL-1 beta, or TNF-alpha concentrations, and the borderline correlation of the former with CRP levels, demonstrate that IL-1ra is an acute phase reactant in RA as well as in SLE patients.

摘要

目的

研究初诊、未经治疗的类风湿关节炎（RA）或系统性红斑狼疮患者单核细胞产生细胞因子的不同能力，并探讨未经治疗的RA患者血清C反应蛋白（CRP）、细胞因子、关节肿胀计数和红细胞沉降率（ESR）之间的可能相关性。

方法

将未经治疗的RA或狼疮患者的单核细胞与脂多糖（LPS，模拟细菌感染）或免疫复合物（模拟内源性免疫偏差）在体外进行培养，收集上清液用于细胞因子测定。检测RA患者血清中的白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、白细胞介素-10、肿瘤坏死因子-α（TNF-α）和白细胞介素-1受体拮抗剂（IL-1ra）。将这些细胞因子与血清CRP、关节肿胀计数和ESR进行关联分析。

结果

RA单核细胞在体外均能产生IL-6、IL-1β、TNF-α或IL-10。相比之下，狼疮单核细胞可分为两个亚群：（i）在LPS刺激下产生细胞因子，但在免疫复合物刺激下不产生的单核细胞；（ii）有趣的是，在免疫复合物刺激下产生细胞因子，但在LPS刺激下不产生的单核细胞。这些细胞因子反过来又刺激肝脏在SLE亚群和RA患者中以不同方式合成CRP。此外，在RA患者中，血清IL-1ra水平与血清IL-6、IL-1β和TNF-α浓度显著相关（p分别为0.005、0.008或0.040），但与IL-10无关（p = 0.582）。

结论

与均一的RA单核细胞不同，存在两个狼疮亚群，它们分别对LPS或免疫复合物产生反应以产生诱导CRP的细胞因子。这是首次报道RA和狼疮单核细胞中诱导CRP产生的细胞因子的不同反应模式可能是RA中CRP水平高而狼疮中异质性低的基础。血清IL-1ra水平与血清IL-6、IL-1β或TNF-α浓度的相关性，以及前者与CRP水平的临界相关性，表明IL-1ra在RA以及SLE患者中都是一种急性期反应物。