THE EMERGING ROLE OF MEDIATORS IN GLOMERU LONEPHRITIS

Pro-inflammatory mediators: They include proteases, reactive oxygen sp ecies, eicosanoids and cytokines. These mediators contribute to reduce the glomerular filtration rate and to amplify the intensity of glomer ular inflammatory cell infiltration. Anti-inflammatory mediators: They include eicosanoids such as lipoxins, specific antagonists such as in terleukin (IL)-1 receptor antagonist neuropoietic cytokines such as IL -6 and leukemia inhibitory factor and deactivators of inflammatory mac rophages such as transforming growth factor-beta (TGF-beta) and IL-10. They limit the effects of pro-inflammatory mediators by blunting thei r synthesis, stability or function. Potential use as therapeutic agent s: Local or systemic administration of anti-inflammatory mediators may provide efficient treatments for experimental glomerulonephritis. For instance, administration of IL-4, IL-1 receptor antagonist or IL-10 r educes glomerular lesions as assessed by measuring the decrease in inf lammatory cell infiltration, fibrin deposition and protein excretion a t the heterologous and/or autologous phase of rat nephrotoxic serum ne phritis. However the efficacy of anti-inflammatory mediators as therap eutic agents is potentially limited by side-effects including exaggera ted humoral immune response and accelerated glomerulosclerosis. (C) 19 98, Masson, Paris.