Lit L C W, Wong C K, Tam L S, Li E K M, Lam C W K
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Ann Rheum Dis. 2006 Feb;65(2):209-15. doi: 10.1136/ard.2005.038315. Epub 2005 Jun 23.
Chemokines are involved in leucocyte chemotaxis. Infiltrating leucocytes play an important role of tissue injury in systemic lupus erythematosus (SLE).
To investigate the role of inflammatory chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis and disease activity.
Plasma concentrations and ex vivo peripheral blood mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1, TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4, and IL10 were assayed in 80 SLE patients with or without renal disease and 40 healthy controls by immunofluorescence flow cytometry and enzyme linked immunosorbent assay.
Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18 concentrations in all SLE patients were higher than in controls, and correlated significantly with SLEDAI score (all p<0.05). In SLE patients without renal disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18 correlated with disease activity (all p<0.05). Plasma IL18 concentration correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their difference in disease activity (all p<0.05). Patients with renal disease had an augmented ex vivo release of RANTES.
The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.
趋化因子参与白细胞趋化作用。浸润的白细胞在系统性红斑狼疮(SLE)的组织损伤中起重要作用。
探讨炎性趋化因子在SLE发病机制和疾病活动中的作用及其与白细胞介素18(IL18)的关系。
采用免疫荧光流式细胞术和酶联免疫吸附测定法,检测80例有或无肾脏疾病的SLE患者及40例健康对照者血浆中炎性趋化因子IP-10、RANTES、MIG、MCP-1、TARC、IL8和GROα以及促炎细胞因子IL18、IFNγ、IL2、IL4和IL10的浓度,以及外周血单个核细胞体外产生这些因子的情况。
所有SLE患者血浆中IP10、RANTES、MIG、MCP-1、GROα和IL18的浓度均高于对照组,且与SLE疾病活动指数(SLEDAI)评分显著相关(均p<0.05)。在无肾脏疾病的SLE患者中,IP10、RANTES、MIG、MCP-1、IL8和IL18与SLEDAI评分呈正相关,而在有肾脏病变的患者中,IP10、IL8、IL10和IL18与疾病活动相关(均p<0.05)。所有SLE患者血浆IL18浓度与IP10、MIG、GROα和IL8呈正相关(均p<0.005)。无论疾病活动程度如何,所有SLE患者经丝裂原诱导后外周血单个核细胞体外产生IP10、MCP-1、TARC、IFNγ、IL4和IL10均增加(均p<0.05)。有肾脏疾病的患者体外RANTES释放增加。
炎性趋化因子血浆浓度升高及体外产生与疾病活动相关,且与IL18有关,这支持了Th1/Th2淋巴细胞和中性粒细胞趋化作用在SLE发病机制中起重要作用的观点。