Immunogold labelling of cytokines in glomeruli in children with various renal diseases.

Precise localization of cytokines such as transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 was observed in glomeruli using immunogold electron microscopy in 21 children with various types of renal diseases. The distribution pattern of these cytokines, as well as immunoglobulins, C3c and fibrinogen (Fg), was essentially confined to the electron-dense deposits (EDDs) regardless of their location. Frequency of positive labelling of each cytokine was different among various types of renal disorder, that is, TGF-beta was found mainly in lupus nephritis (LN), membranous nephropathy and IgA nephropathy, TNF-alpha in LN, and IL-1 in Henoch-Schönlein purpura nephritis. IL-6 was detected only in 1 case of LN. TNF-alpha was also found in the cytoplasm of glomerular epithelial cells. Furthermore, in order to evaluate the relation of cytokines to mesangial expansion, extracellular matrix components such as type IV collagen, laminin and fibronectin were stained. The result was that there was no significant correlation between the signal intensity or distribution pattern of cytokines and that of extracellular matrix components. These findings indicate that these cytokines could be associated with the formation of EDDs together with immunoglobulins, C3c and Fg. The involvement of each cytokine in renal pathophysiology might also depend upon the type of renal disease. They also raise the possibility that the glomerular epithelial cells might produce or absorb TNF-alpha. However, these results did not show significant correlation between cytokine involvement and mesangial expansion.