Heufelder A E, Bahn R S
Department of Internal Medicine, Mayo Clinic/Foundation, Rochester, MN 55905.
Eur J Clin Invest. 1993 Jan;23(1):10-7. doi: 10.1111/j.1365-2362.1993.tb00712.x.
Paracrine interactions between fibroblasts residing in the retro-ocular space and infiltrating lymphocytes/macrophages are thought to be of central importance in the pathogenesis of Graves' ophthalmopathy (GO). Although various roles have been suggested for interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) in GO, their actual presence in Graves' retro-ocular connective tissue has not been demonstrated. We examined surgical specimens obtained during orbital decompression from patients with severe GO (n = 6), and from normal individuals (n = 5), for the presence of IFN gamma, TNF alpha and IL-1 alpha. We used immunohistochemical methods on frozen tissue sections and primary fibroblast cultures, and sodium dodecylsulfate polyacrylamide-gel electrophoresis of tissue extracts and tissue culture supernatants. In addition, immunohistochemical staining of tissues for characterization of the mononuclear cell infiltrates was performed. Aggregates of mononuclear cells in retro-ocular connective and fatty tissue were found in five of six GO tissue specimens, but in none of the control specimens. We detected immunoreactivity for the three cytokines (IFN gamma, TNF alpha and IL-1 alpha) in the five GO tissue specimens that contained mononuclear cell aggregates. In addition, IL-1 alpha immunoreactivity was demonstrable in primary and subsequent GO fibroblast cultures and in their supernatants. In contrast, no immunoreactivity for any of these cytokines was detected in tissue specimens, primary cultures or culture supernatants derived from normal individuals. The presence of mononuclear cell infiltrates and associated immunoreactivity for IFN gamma, TNF alpha, IL-1 alpha in retro-ocular connective tissue derived from patients with GO suggests that the previously demonstrated in vitro functions of these cytokines may indeed be operative in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
眼眶后间隙中的成纤维细胞与浸润的淋巴细胞/巨噬细胞之间的旁分泌相互作用被认为在格雷夫斯眼病（GO）的发病机制中至关重要。尽管干扰素-γ（IFNγ）、肿瘤坏死因子-α（TNFα）和白细胞介素-1α（IL-1α）在GO中被认为具有多种作用，但它们在格雷夫斯眼眶后结缔组织中的实际存在尚未得到证实。我们检查了严重GO患者（n = 6）和正常个体（n = 5）在眼眶减压手术中获得的标本，以检测IFNγ、TNFα和IL-1α的存在。我们对冷冻组织切片和原代成纤维细胞培养物进行了免疫组织化学方法，并对组织提取物和组织培养上清液进行了十二烷基硫酸钠聚丙烯酰胺凝胶电泳。此外，还对组织进行了免疫组织化学染色以鉴定单核细胞浸润的特征。在六个GO组织标本中的五个中发现眼眶后结缔组织和脂肪组织中有单核细胞聚集，但对照标本中均未发现。我们在五个含有单核细胞聚集的GO组织标本中检测到了这三种细胞因子（IFNγ、TNFα和IL-1α）的免疫反应性。此外，IL-1α免疫反应性在GO原代及后续成纤维细胞培养物及其上清液中也得到了证实。相比之下，在正常个体的组织标本、原代培养物或培养上清液中未检测到这些细胞因子的任何免疫反应性。GO患者眼眶后结缔组织中单核细胞浸润以及IFNγ、TNFα、IL-1α相关免疫反应性的存在表明，这些细胞因子先前在体外所证实的功能在体内可能确实起作用。（摘要截断于250字）
