Simon Diana, Denniston Alastair K O, Tomlins Paul J, Wallace Graham R, Rauz Saaeha, Salmon Mike, Murray Philip I, Curnow S John
Institute of Biomedical Research, MRC Centre for Immune Regulation, Division of Immunity and Infection, Medical School, The University of Birmingham, Birmingham, United Kingdom.
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3988-91. doi: 10.1167/iovs.08-1953. Epub 2008 May 9.
To determine the concentrations of soluble gp130, a natural antagonist of IL-6 transsignaling, in the serum and aqueous humor (AqH) of patients with uveitis.
Serum was obtained from the peripheral blood of patients with active uveitis and healthy control subjects. AqH samples were collected from patients with active uveitis and those without uveitis who were undergoing routine cataract surgery. Samples were centrifuged and the cell-free supernatant frozen at -80 degrees C. Concentrations of sgp130, sIL-6R, and IL-6 were determined by a sandwich ELISA or multiplex bead immunoassay, using standard curves of known concentrations of recombinant cytokines.
Serum concentrations of sgp130 were not significantly different between control individuals and patients with active anterior uveitis, regardless of the degree of intraocular inflammation cells. By contrast, the concentration of sgp130 in AqH was very low in patients with no or little inflammation, but increased significantly with disease severity. The greatest elevations of AqH sgp130 were found in patients with the highest cellular activity. Simultaneous measurement of IL-6, sIL-6R, and sgp130 revealed a high degree of correlation between the levels of these molecules, especially for sIL-6R and sgp130.
Soluble gp130 is increased in the AqH of patients with active uveitis. It is likely that sgp130 partially inhibits the process of IL-6 transsignaling during inflammation. However, the concentration found is still far below that in serum, suggesting that increasing the level of sgp130 further may assist in reducing the inflammatory changes induced by IL-6 transsignaling.
测定葡萄膜炎患者血清和房水中可溶性gp130(IL-6转信号传导的天然拮抗剂)的浓度。
从活动性葡萄膜炎患者的外周血和健康对照者中获取血清。从活动性葡萄膜炎患者以及正在接受常规白内障手术的非葡萄膜炎患者中采集房水样本。样本离心后,将无细胞上清液在-80℃下冷冻。使用已知浓度的重组细胞因子标准曲线,通过夹心ELISA或多重珠免疫测定法测定sgp130、sIL-6R和IL-6的浓度。
无论眼内炎症细胞程度如何,对照个体和活动性前葡萄膜炎患者的血清sgp130浓度均无显著差异。相比之下,无炎症或炎症轻微的患者房水中sgp130浓度非常低,但随着疾病严重程度显著升高。在细胞活性最高的患者中,房水sgp130升高最为明显。同时测量IL-6、sIL-6R和sgp130发现,这些分子水平之间存在高度相关性,尤其是sIL-6R和sgp130。
活动性葡萄膜炎患者房水中可溶性gp130增加。sgp130可能在炎症期间部分抑制IL-6转信号传导过程。然而,所测得的浓度仍远低于血清中的浓度,这表明进一步提高sgp130水平可能有助于减少IL-6转信号传导引起的炎症变化。