Anti-inflammatory lymphokine mRNA expression in antibody-induced glomerulonephritis.
T-helper subset 2 (Th2) lymphocytes produce interleukin 4 (IL-4) and IL-10, which exert anti-inflammatory actions on monocytes and macrophages. Th1 lymphocytes, on the other hand, secrete interferon-gamma (IFN gamma) which promotes tissue inflammation. The functional dichotomy between TH1 and Th2 lymphocyte subsets suggests that these cells play a regulatory role in inflammatory disease. The participation of Th subpopulations and their lymphokine products in experimental glomerulonephritis (GN) has not been previously evaluated. In this study, we examined renal expression of Th1 and Th2-type lymphokines in the first 48 hours of passive anti-glomerular basement membrane (anti-GBM) GN in the rate. Using the reverse transcriptase-polymerase chain reaction (RT-PCR) method, apparent increase in expression of both TH1-type (IL-2 and IFN gamma) and Th2-type (IL-4 and IL-10) lymphokine mRNA was observed in glomerular-enriched renal tissue obtained from nephritic rats. Induction of monocyte-derived IL-1 alpha and IL-1 receptor antagonist (IL-1RA) mRNA expression was also detected shorted after initiation of GN. Evidence for influx of mononuclear cells including T lymphocytes into the kidney was noted during the same time period as cytokine mRNA expression. 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 protein production in the kidney during antibody-mediated GN. WE hypothesize that Th lymphocyte subsets modulate glomerular inflammation by producing lymphokines with opposing actions.
Lakkis
F G
FG
Renal Division, Emory University School of Medicine, Atlanta, Georgia, USA.
Baddoura
F K
FK
Cruet
E N
EN
Parekh
K R
KR
Fukunaga
M
M
Munger
K A
KA
D000818:Animals; D000911:Antibodies, Monoclonal; D015139:Blotting, Southern; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007378:Interleukins; D012333:RNA, Messenger