Inflammatory cytokines in glomerulonephritis

SUMMARY: The importance of various inflammatory cytokines in mediating renal disease is now recognized, and the potential for the use of cytokine blockade as a therapeutic intervention is under active investigation. Studies in rat anti‐glomerular basement membrane (GBM) disease model showed that antagonism of the proinflammatory cytokine IL‐1 inhibited induction of glomerulonephritis, and prevented progression of established disease. A second cytokine Tumour Necrosis Factor‐alpha (TNF‐α) had similar proinflammatory effects to IL‐1 in this model. Blocking the actions of both cytokines together, however, had no added benefit. Another cytokine Macrophage Migration Inhibitory Factor (MIF) has been shown to override the anti‐inflammatory effects of corticosteriods. Renal MIF is markedly up‐regulated in rat anti‐GBM disease and blocking studies have demonstrated MIF plays a pathological role in mediating renal injury in this model. the importance of MIF in glomerulonephritis has been demonstrated by the fact that MIF is produced locally within the kidney, that it reflects the severity of the cellular immune response, and can be measured in the urine. Macrophage Migration Inhibitory Factor is up‐regulated in human glomerular disease and correlates with loss of renal function and is thus a potential target for therapy for human glomerulonephritis. Thus, the inflammatory cytokines, IL 1, TNF‐α and MIF each play a role in the immune/inflammatory process in glomerulonephritis. Blocking their action reduces disease and cytokine blocking agents have therapeutic potential.