Fukatsu A, Matsuo S, Yuzawa Y, Miyai H, Futenma A, Kato K
First Department of Internal Medicine, Aichi Medical University, Japan.
Lab Invest. 1993 Jul;69(1):58-67.
Interleukin-6 (IL-6) exerts multiple effects on infiltrated inflammatory cells and on structural cells in tissues. We previously reported that IL-6 expression is increased in the area of glomerular and tubular inflammation and tubular atrophy (Lab Invest 65:61, 1991). In the present study, we investigated the expression of IL-6 and HLA molecules in the tubules of patients with renal diseases, and correlate it with the morphological findings.
Specific monoclonal antibodies and indirect immunofluorescence microscopy were used to identify IL-6, HLA-ABC, and -DR molecules, CD-2+ and CD-8+ lymphocytes and macrophages, in renal tissues obtained by biopsy from 41 patients that were divided into three groups on the basis of clinical, functional, and histologic findings. Group 1 included 12 patients with signs of acute renal disease and prevalent acute tubulointerstitial lesions. Group 2 included 19 patients with signs of chronic renal disease and histologic lesions of glomerulo- and tubulointerstitial nephritis. Group 3 included 10 patients that developed an acute renal disease treated with corticosteroids. When the acute symptoms subsided and the renal biopsy was performed, lesions characteristic of chronic tubulointerstitial nephritis were found.
IL-6 was localized in all or in some cells of injured proximal tubules, including atrophic tubules. In one-third of specimens, there was more IL-6 in tubular cells than in infiltrated cells. The strongest expression of IL-6, HLA-ABC, and DR molecules was found in group 1, and the weakest in group 3. In the area with tubulointerstitial lesions, tubular IL-6 colocalized with HLA-ABC. Colocalization of IL-6 and HLA-DR was more evident in tubulointerstitial lesions of patients in group 2. In both groups 1 and 2, the distribution of IL-6 was statistically correlated with that of HLA-ABC and with interstitial infiltration of inflammatory cells. In group 2, there was statistical correlation between the expression of IL-6 and HLA-DR. The expression of IL-6 and of HLA molecules decreased in group 3.
These results suggest that tubular IL-6 may be involved in the pathogenesis of tubulointerstitial nephritis.
白细胞介素-6（IL-6）对浸润的炎症细胞和组织中的结构细胞具有多种作用。我们之前报道过，在肾小球和肾小管炎症及肾小管萎缩区域，IL-6表达增加（《实验医学杂志》65:61，1991年）。在本研究中，我们调查了肾病患者肾小管中IL-6和HLA分子的表达，并将其与形态学结果相关联。
使用特异性单克隆抗体和间接免疫荧光显微镜来识别41例患者肾组织中的IL-6、HLA-ABC和-DR分子、CD-2 +和CD-8 +淋巴细胞以及巨噬细胞。这些患者根据临床、功能和组织学结果分为三组。第1组包括12例有急性肾病体征且以急性肾小管间质病变为主的患者。第2组包括19例有慢性肾病体征且有肾小球和肾小管间质性肾炎组织学病变的患者。第3组包括10例因接受皮质类固醇治疗而出现急性肾病的患者。当急性症状消退并进行肾活检时，发现了慢性肾小管间质性肾炎的特征性病变。
IL-6定位于受损近端肾小管的所有或部分细胞中，包括萎缩的肾小管。在三分之一的标本中，肾小管细胞中的IL-6比浸润细胞中的更多。IL-6、HLA-ABC和DR分子的最强表达见于第1组，最弱表达见于第3组。在肾小管间质病变区域，肾小管IL-6与HLA-ABC共定位。IL-6和HLA-DR的共定位在第2组患者的肾小管间质病变中更明显。在第1组和第2组中，IL-6的分布与HLA-ABC的分布以及炎症细胞的间质浸润在统计学上相关。在第2组中，IL-6的表达与HLA-DR之间存在统计学相关性。第3组中IL-6和HLA分子的表达降低。
这些结果表明，肾小管IL-6可能参与肾小管间质性肾炎的发病机制。
