ヒト増殖性糸球体疾患におけるインターロイキン6の腎組織内分布

Abstract

The present study was designed to clarify the relationship between the intrarenal distribution of interleukin-6 (IL-6), urinary IL-6 activity, clinical features and renal pathology in human proliferative glomerulonephritides. Nine specimens of normal kidney tissue from surgically resected kidney and 59 renal biopsy specimens obtained from 43 patients with mesangial proliferative glomerulonephritis (mesPGN), including IgA nephropathy (IgA-GN) and non-IgA nephropathy (non-IgA-GN), and 16 cases of lupus nephritis (LN) were examined by indirect immunofluorescence microscopy using monoclonal antibody specific to human recombinant IL-6. In addition, urinary IL-6 activity was measured using an IL-6 dependent murine hybridoma clone, MH60. BSF2. In both the normal kidney and the diseased kidney, IL-6 was observed in the mesangial area in a fine granular fashion and visible in cytoplasma of both visceral epithelial cells and Bowman's epithelial cells. IL-6 was also observed in vascular smooth muscle cells. However, IL-6 was decreased in intensity in sclerotic lesions. In diseased kidneys, IL-6 was found in atrophic tubules. The grade of mesangial IL-6 staining correlated significantly with the degree of mesangial proliferation. Moreover, the grade of mesangial IL-6 staining tended to show an inverse relationship with the positive number of visceral epithelial cells. Urinary IL-6 activity increased significantly in proportion to the degree of mesangial proliferation as well as the grade of mesangial IL-6 staining. In patients with mesPGN, urinary IL-6 activity showed a significant correlation with the severity of the tubulointerstitial lesion. Finally, in patients with IgA-GN, there appeared no obvious relationship between the distribution of IL-6 and that of IgA in the double immunofluorescence. These results suggest that the grade of mesangial IL-6 staining and urinary IL-6 activity reflect the severity of mesangial proliferation, and that IL-6 may play an important role in human proliferative glomerulonephritides.