EXPRESSION OF CYTOKINES AND GROWTH-FACTORS IN HUMAN GLOMERULONEPHRITIDES

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, fro m the various autocrine and paracrine mediators identified in vitro an d in animal models, so far only a few have been demonstrated in select ed human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodi es (ANCA), an example of an acute form of GN, and mesangial IgA GN, us ually a chronic form of GN, with immunocytochemistry, in situ hybridiz ation and the polymerase chain reaction. Normal renal tissue from tumo ur nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrat ing mononuclear cells in glomeruli and in the interstitium expressed i nterleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, IL-2, inter feron (IFN)-gamma, platelet-derived growth factor (PDGF) and transform ing growth factor (TGF)-beta. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epith elial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cy tokine and growth factor receptors TNF-R, IL-IR type II, IL-2R, IFN-ga mmaR and PDGFbeta-R. In contrast, in mesangial IgA-GN, IL-1beta, TNF-a lpha, IFN-gamma and IL-2 were usually absent in glomeruli. Mesangial e xpansion in this disorder was accompanied by an increased expression o f PDGF, PDGFbeta-R, TGF-beta and IL-6 in mesangial areas. In both cond itions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistr y). These results demonstrate that different cytokine and growth facto r patterns are expressed in the various forms of GN, and suggest that the local production of these peptides plays an important role in the pathogenesis and progression of human glomerulonephritides.