Nureki Shin-ichi, Miyazaki Eishi, Ando Masaru, Ueno Takuya, Fukami Tetsujiro, Kumamoto Toshihide, Sugisaki Katsunori, Tsuda Tomiyasu
Division of Pulmonary Disease, Third Department of Internal Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
Respir Med. 2008 Feb;102(2):239-47. doi: 10.1016/j.rmed.2007.09.006. Epub 2007 Oct 18.
In sarcoidosis, the T helper type 1 (Th1) response tends to predominate at affected disease sites; however, whether Th1/Th2 polarization occurs in the peripheral circulation is unknown.
Fifty-two patients with sarcoidosis and 21 healthy volunteers were investigated. The concentrations of interferon-inducible protein 10 (IP-10)/CXCL10 and thymus- and activation-regulated chemokine (TARC)/CCL17 in the serum, bronchoalveolar lavage fluid (BALF) and culture supernatant were measured by an enzyme-linked immunosorbent assay. The circulating CXCR3+ CD4+ T cells and CCR4+ CD4+ T cells were assessed by flow cytometry.
The CXCR3- or CCR4-positive ratios among CD4+ T cells were both higher in sarcoidosis than in healthy volunteers. The serum levels of both IP-10 and TARC of the patients with sarcoidosis were significantly higher than those of the healthy volunteers. In patients with sarcoidosis, a larger amount of IP-10 was generated by the BALF cells, whereas IP-10 production by peripheral blood mononuclear cells did not increase in comparison to the control subjects. The TARC levels produced by peripheral blood mononuclear cells of sarcoidosis patients were significantly higher than those of the controls, while no difference existed between the 2 groups regarding TARC production by BALF cells.
IP-10 is mainly produced at the lung and TARC in the peripheral circulation in sarcoidosis patients. Both IP-10 and TARC cooperatively play a role in the pathogenesis of sarcoidosis.
在结节病中,1型辅助性T细胞(Th1)反应往往在受影响的疾病部位占主导;然而,外周循环中是否发生Th1/Th2极化尚不清楚。
对52例结节病患者和21名健康志愿者进行了研究。采用酶联免疫吸附测定法测量血清、支气管肺泡灌洗液(BALF)和培养上清液中干扰素诱导蛋白10(IP-10)/CXCL10和胸腺与活化调节趋化因子(TARC)/CCL17的浓度。通过流式细胞术评估循环中的CXCR3 + CD4 + T细胞和CCR4 + CD4 + T细胞。
结节病患者CD4 + T细胞中CXCR3或CCR4阳性率均高于健康志愿者。结节病患者的血清IP-10和TARC水平均显著高于健康志愿者。在结节病患者中,BALF细胞产生的IP-10量更大,而与对照组相比,外周血单个核细胞产生的IP-10没有增加。结节病患者外周血单个核细胞产生的TARC水平显著高于对照组,而两组之间BALF细胞产生TARC的情况没有差异。
在结节病患者中,IP-10主要在肺部产生,而TARC在外周循环中产生。IP-10和TARC在结节病的发病机制中共同发挥作用。