INTRARENAL SYNTHESIS OF IL-6 IN IGA NEPHROPATHY

Recent in vitro studies have shown the synthesis of interleukin-6 (IL- 6) in glomerular mesangial and epithelial cells, and suggested the inv olvement of IL-6 in mesangial proliferative glomerulonephritis. Howeve r, the expression site of IL-6 mRNA in renal tissue of IgA nephropathy (IgAN), the most common chronic mesangial proliferative glomeruloneph ritis, remains obscure. To localize IL-6 mRNA in renal biopsy specimen s of IgAN, we used nonradioactive in situ hybridization (ISH) develope d in our laboratory, sensitive in detecting individual cells positive for a specific mRNA. In some sections, periodic acid-Schiff staining w as performed after ISH in order to identify the topographical relation between IL-6 mRNA positive cells and glomerular basement membrane and mesangial area. In situ hybridization for IL-6 mRNA and immunohistoch emistry for CD3 and CD68, markers for lymphocytes and monocytes, respe ctively, were also performed on serial sections to examine the contrib ution of infiltrated mononuclear cells to cells positive for IL-6 mRNA in glomeruli. Glomerular resident cells, including glomerular mesangi al and epithelial cells and cells of Bowman's capsule, as well as tubu lar epithelial cells and infiltrated mononuclear cells expressed IL-6 mRNA. We also compared the localization of IL-6 mRNA and protein and s howed different distribution between the gene product and protein, The expression of IL-6 mRNA correlated with the degree of mesangial cell proliferation and tubulointerstitial changes. Our results indicate tha t IL-6 is synthesized in renal tissues of IgAN and suggest that the in creased IL-6 expression may be important in the pathogenesis of IgAN.