Blain Hubert, Abdelmouttaleb Idritia, Belmin Joël, Blain Arielle, Floquet Jacques, Guéant Jean-Louis, Jeandel Claude
Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France.
J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):M241-5. doi: 10.1093/gerona/57.4.m241.
Giant cell arteritis (GCA) is a subacute periarteritis predominantly affecting segments of the external carotids of elderly patients. Vasculitic lesions in GCA samples might be characterized by in situ production of cytokines mRNA, indicative of macrophage and T-cell activation. However, whether the cytokine production of vessels with arteritis differs from that of vessels exposed to inflammatory conditions that originate peripheral to the vessel remains unknown.
We investigated cytokine and soluble receptor cytokine production in blood samples and cultures of human temporal arteries from 22 consecutive patients (mean age 77 +/- 6 years) further investigated for possible diagnosis of GCA: 7 patients had GCA and 15 had neither GCA nor vasculitis but had other inflammatory, infectious, or malignant diseases (controls). The production of cytokines and soluble cytokine receptors in the supernatants of cultures of 3-mm segments of temporal artery specimens, before and after lipopolysaccharide (LPS) stimulation (10 ng/ml and 10 microg/ml) and in serum, was quantified using sandwich enzyme-linked immunosorbent assay (ELISA).
Cytokine production by temporal arteries increased significantly and in a dose-dependent manner (p <.01) after LPS stimulation in all patients studied, suggesting that the system is methodologically functional. Despite a large interindividual variation, we found similar differences in cytokine production before and after stimulation by 10 ng/ml and 10 microg/ml LPS between both groups: temporal arteries of GCA patients produced more interleukin (IL)-1beta (p <.05) and IFNgamma (nonsignificant) and less tumor necrosis factor (TNF)alpha (p <.05) and IL-6 (nonsignificant) than temporal arteries of controls. The levels of TNFalpha (p <.05) and IL-6 soluble receptor (p <.05) were significantly lower in GCA patients as compared with controls in blood samples, whereas levels of cytokines in temporal artery and in blood samples were not significantly correlated at the individual level in both groups.
The present pilot study, which requires further confirmation on a larger number of well-defined patients with GCA, suggests that a specific arterial cytokine production profile might exist in GCA (high IL-1beta +/- IFNgamma and low TNFalpha), addresses the question of the mechanisms by which IL-1beta and TNFalpha might be differentially regulated at the level of the arterial cell wall, and supports the view that cultures of the temporal artery might be an interesting tool for evaluating the role of cytokines in GCA pathogenesis.
巨细胞动脉炎（GCA）是一种主要影响老年患者颈外动脉各段的亚急性动脉周围炎。GCA样本中的血管炎性病变可能以细胞因子mRNA的原位产生为特征，这表明巨噬细胞和T细胞被激活。然而，患有动脉炎的血管的细胞因子产生是否与暴露于血管外周起源的炎症条件下的血管不同，仍不清楚。
我们调查了22例连续患者（平均年龄77±6岁）的血液样本以及颞浅动脉培养物中细胞因子和可溶性受体细胞因子的产生情况，这些患者进一步接受了GCA可能诊断的检查：7例患有GCA，15例既没有GCA也没有血管炎，但患有其他炎症、感染或恶性疾病（对照组）。使用夹心酶联免疫吸附测定（ELISA）对颞浅动脉标本3毫米节段培养上清液在脂多糖（LPS）刺激（10纳克/毫升和10微克/毫升）前后以及血清中细胞因子和可溶性细胞因子受体的产生进行定量。
在所有研究患者中，LPS刺激后颞浅动脉的细胞因子产生显著增加且呈剂量依赖性（p<.01），这表明该系统在方法学上是有功能的。尽管个体间差异很大，但我们发现两组在10纳克/毫升和10微克/毫升LPS刺激前后细胞因子产生的差异相似：与对照组的颞浅动脉相比，GCA患者的颞浅动脉产生更多的白细胞介素（IL）-1β（p<.05）和干扰素γ（无显著性差异），而肿瘤坏死因子（TNF）α（p<.05）和IL-6（无显著性差异）产生较少。与对照组相比，GCA患者血液样本中TNFα（p<.05）和IL-6可溶性受体（p<.05）的水平显著较低，而两组中颞浅动脉和血液样本中的细胞因子水平在个体水平上无显著相关性。
本初步研究需要在更多明确诊断的GCA患者中进一步证实，提示GCA可能存在特定的动脉细胞因子产生谱（高IL-1β±干扰素γ和低TNFα），提出了IL-1β和TNFα在动脉壁水平可能受到不同调节的机制问题，并支持颞浅动脉培养可能是评估细胞因子在GCA发病机制中作用的一个有趣工具的观点。
