EXPRESSION OF INTERLEUKIN-6 AND MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES IN TUBULAR EPITHELIAL-CELLS OF DISEASED HUMAN KIDNEYS

BACKGROUND: Interleukin-6 (IL-6) exerts multiple effects on infiltrate d 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 correlat e it with the morphological findings. EXPERIMENTAL DESIGN: Specific mo noclonal antibodies and indirect immunofluorescence microscopy were us ed to identify IL-6, HLA-ABC, and -DR molecules, CD-2+ and CD-8+ lymph ocytes and macrophages, in renal tissues obtained by biopsy from 41 pa tients that were divided into three groups on the basis of clinical, f unctional, and histologic findings. Group 1 included 12 patients with signs of acute renal disease and prevalent acute tubulointerstitial le sions. Group 2 included 19 patients with signs of chronic renal diseas e and histologic lesions of glomerulo- and tubulointerstitial nephriti s. 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 tubuloi nterstitial nephritis were found. RESULTS: IL-6 was localized in all o r in some cells of injured proximal tubules, including atrophic tubule s. In one-third of specimens, there was more IL-6 in tubular cells tha n 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 H LA-ABC. Colocalization of IL-6 and HLA-DR was more evident in tubuloin terstitial lesions of patients in group 2. In both groups 1 and 2, the distribution of IL-6 was statistically correlated with that of HLA-AB C 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 grou p 3. CONCLUSIONS: These results suggest that tubular IL-6 may be invol ved in the pathogenesis of tubulointerstitial nephritis.