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 side effects. The cellular and molecular basis of acute and chronic inflammation is increasingly understood and the work in a number of animal models of 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 interactions. Within damaged tissue it is possible to decrease the activity of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) by using their natural antagonists, namely interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptors. In addition the behaviour of macrophages can be altered by the effects of anti-inflammatory cytokines 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 clinical practice remains elusive, however the prospect of using gene transfer technology to deliver anti-inflammatory factors directly to the site of inflammation and our increasing understanding of the complexity of the control of inflammation bring such therapies closer.
Kluth
D C
DC
Department of Medicine and Therapeutics, University of Aberdeen, UK.
Rees
A J
AJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005921:Glomerulonephritis / Q000188:drug therapy*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000627:therapeutic use; D015847:Interleukin-4 / Q000627:therapeutic use; D015850:Interleukin-6 / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D007375:Interleukin-1; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4