Influence of TH1/TH2 switched immune response on renal ischemia-reperfusion injury.
OBJECTIVE
Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1).


METHODS
We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery.


CONCLUSIONS
The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1.
Marques
Vilmar Paiva
VP
Laboratório de Imunologia Clínica e Experimental, Division of Nephrology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
Gonçalves
Giselle Martins
GM
Feitoza
Carla Quarin
CQ
Cenedeze
Marcos Antonio
MA
Fernandes Bertocchi
Ana Paula
AP
Damião
Marcio Jose
MJ
Pinheiro
Helady Sanders
HS
Antunes Teixeira
Vicente Paula
VP
dos Reis
Marlene Antônia
MA
Pacheco-Silva
Alvaro
A
Saraiva Câmara
Niels Olsen
NO
D058186:Acute Kidney Injury / Q000276:immunology*; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D018664:Interleukin-12 / Q000172:deficiency; D015847:Interleukin-4 / Q000172:deficiency; D007668:Kidney / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012038:Regeneration / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology*; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D018664:Interleukin-12; D015847:Interleukin-4; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse