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 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.

EXPERIMENTAL DESIGN

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.

RESULTS

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.

CONCLUSIONS

These results suggest that tubular IL-6 may be involved in the pathogenesis of tubulointerstitial nephritis.