Interleukin-4 ameliorates experimental glomerulonephritis and up-regulates glomerular gene expression of IL-1 decoy receptor.
Monocytes/macrophages and pro-inflammatory cytokines such as interleukin (IL)-1 are important in the pathogenesis of acute glomerulonephritis. The aim of this study was to examine whether IL-4, a cytokine with anti-inflammatory activity, could modulate glomerular inflammation and reduce injury in vivo. Treatment with recombinant rat IL-4 in a model of anti-glomerular basement membrane (GBM) antibody mediated glomerulonephritis in rats reduced glomerular injury. Albuminuria was less (73% less at day 4) and a lower proportion of glomeruli had capillary thrombi (79% less at day 4). In IL-4 treated rats, there was a moderate reduction in the number of macrophages in the glomeruli and also suppression of pro-inflammatory activities of the macrophages. Northern blot analysis of glomerular RNA showed that treatment with IL-4 up-regulated mRNA levels of type II IL-1 receptor (IL-1RTII). IL-1RTII, also known as IL-1 decoy receptor, may act as a decoy molecule to inhibit the effect of IL-1 beta. To our knowledge, this is the first demonstration of (i) recombinant IL-4 reducing glomerular inflammation in vivo and (ii) a treatment that increases IL-1RTII expression in association with reduction of tissue injury in vivo.
Tam
F W
FW
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, England. ftam@rpms.ac.uk
Smith
J
J
Karkar
A M
AM
Pusey
C D
CD
Rees
A J
AJ
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism / Q000628:therapy*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015847:Interleukin-4 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology
D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D015847:Interleukin-4