INVOLVEMENT OF IL-4 IN HUMAN GLOMERULONEPHRITIS - AN IN-SITU HYBRIDIZATION STUDY OF IL-4 MESSENGER-RNA AND IL-4 RECEPTOR MESSENGER-RNA

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 recept or (IL-4R) in human kidney has not been fully determined. Nonradioacti ve in situ hybridization was used to examine the expression of IL-4 mR NA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL- 4R mRNA, whereas in diseased glomeruli both mRNA types were strongly e xpressed in resident glomerular cells, including mesangial cells glome rular epithelial cells, and cells of the Bowman's capsule. The relatio nship between the expression of these mRNA and the degree of glomerula r injury was different in different types of glomerulonephritis. In Ig A nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hyp ercellularity and extracellular matrix expansion. However, IL-4R expre ssion was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these m RNA forms were observed in individual cells. In tubulointerstitium wit h severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic t ubules and some of the infiltrating cells and fibroblasts. The interst itial expression of these mRNA farms was similar in IgA nephropathy, n on-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulointerstitial chang es. These results suggest that an autocrine and/or paracrine pathway o f IL-4 is present in human diseased kidneys and that IL-4 may be invol ved in tissue injury in glomerulonephritis.