ANTIINFLAMMATORY LYMPHOKINE MESSENGER-RNA EXPRESSION IN ANTIBODY-INDUCED GLOMERULONEPHRITIS

T helper subset 2 (Th2) lymphocytes produce interleukin 4 (IL-4) and I L-10, which exert anti-inflammatory actions on monocytes and macrophag es. Th1 lymphocytes, on the other hand, secrete interferon-gamma (IFN gamma) which promotes tissue inflammation. The functional dichotomy be tween Th1 and Th2 lymphocyte subsets suggests that these cells play a regulatory role in inflammatory disease. The participation of Th subpo pulations and their lymphokine products in experimental glomerulonephr itis (GN) has not been previously evaluated. In this study, we examine d renal expression of Th1 and Th2-type lymphokines in the first 48 hou rs of passive anti-glomerular basement membrane (anti-GEM) GN in the r at. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) method, apparent increase in expression of both Th1-type (IL-2 and IF N gamma) and Th2-type (IL-4 and IL-10) lymphokine mRNA was observed in glomerular-enriched renal tissue obtained from nephritic rats. Induct ion of monocyte-derived IL-1 alpha and IL-1 receptor antagonist (IL-1R A) mRNA expression was also detected shortly after initiation of GN. E vidence for influx of mononuclear cells including T lymphocytes into t he kidney was noted during the same time period as cytokine mRNA expre ssion. Utilizing a monoclonal anti-rat IL-4 antibody, we also detected interleukin 4-producing cells in the renal cortex 24 hours following induction of GN. These experiments demonstrate for the first time anti -inflammatory lymphokine (IL-4 and IL-10) mRNA expression and IL-4 pro tein production in the kidney during antibody-mediated GN. We hypothes ize that Th lymphocyte subsets modulate glomerular inflammation by pro ducing lymphokines with opposing actions.