New approaches to modify glomerular inflammation

Glomerulonephritis remains the leading cause of end-stage renal failure and treatments for these conditions remain non-specific and with significant s ide effects. The cellular and molecular basis of acute and chronic inflamma tion is increasingly understood and the work in a number of animal models o f nephritis demonstrates the potential of specific molecular interventions. These include preventing the migration of inflammatory cells by inhibiting the effects of chemokines or blocking endothelial/leucocyte adhesion inter actions. Within damaged tissue it is possible to decrease the activity of p ro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) by using their natural antagonists, namely interleukin-1 rece ptor antagonist (IL-1ra) and soluble TNF receptors, In addition the behavio ur of macrophages can be altered by the effects of anti-inflammatory cytoki nes including interleukin-4 (IL-4), interleukin-13 (IL-13), interleukin-10 (IL-10), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta ), By deactivating the inflammatory response of macrophages these cytokines can favour resolution of disease. The ability to use these approaches in c linical practice remains elusive, ho however the prospect of using gene tra nsfer technology to deliver anti-inflammatory factors directly to the site of inflammation and our increasing understanding of the complexity of the c ontrol of inflammation bring such therapies closer.