DEFICIENCY OF IL-10/IL-12 CYTOKINES EXACERBATE SYSTEMIC INFLAMMATORY RESPONSES IN RENAL INJURIES INDUCED BY ISCHEMIA AND REPERFUSION
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1
University of Bonn, Institute Reconstructive Neurobiology, Life&Brain center, Germany
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2
Federal University of São Paulo, Departament of Medicine, Nephrology Division, Brazil
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3
University of São Paulo, Departament of Immunology, Laboratory Transplantation Immunobiology, Brazil
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4
Federal University of Uberaba, Brazil
Renal ischemia/reperfusion injury (IRI) is the major cause of acute kidney injury (AKI) in native and transplanted kidneys, with a complex pathogenesis involving many components of inflammatory response such as leukocyte infiltration and release of inflammatory mediators by tubular cells. Recent evidences have shown a critical role of the CD4+ T cells, with a balance between Th1/Th2 cells as a possible effectors mechanism. In order to evaluate the role of Th1/Th2 immune response in this system, IL-12, IL-4, IL-10 deficient mice and IL-12/IL-10 double deficient mice were used. Moreover, for adoptive transference studies we generated chimeric mice on C57BL/6 background. Data was collected 24 hours post IRI. Renal function was evaluated by serum urea measurement and renal morphometric histology analyses. Gene expression of IL-6, MCP-1 and HO-1 were also investigated. Strikingly, IL-4, IL-10 and IL-12/IL-10 KO deficient animals presented higher renal dysfunction when compared to controls followed by higher expression of HO-1, IL-6 and MCP-1. Conversely, IL-12 KO and (IL-12 KO → WT) chimeric mice animals were absolutely protected from IRI. We also observed in the (IL-12 KO → WT) chimeric mice a reduction in urea levels, a better renal outcome and down-regulation in IL-6 expression when compared with WT → WT chimeras, suggesting an indirect role of Th1 response. Moreover, IL-6 was not detected in the serum of IL-12 deficient mice while neutrophil-recruiting chemokine KC was elevated in IL-4, IL-10 and IL-2/IL10 KO deficient mice. Yet, IL-4 was absent in IL-10 and IL-12/IL-10 KO deficient mice serum. Thus our results confirm that Th1/Th2 related cytokines are critically involved during renal IRI.
Acknowledgements
FAPESP (2006/04029-0) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)
Keywords:
Acute renal failure,
ischemia and reperfusion injury,
Cytokines,
il-12,
IL-6,
HO-1,
MCP-1,
KC.
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Paiva
VN,
Monteiro
RM,
Larocca
RA,
Semedo
P,
Dos Reis
MA,
Pacheco-Silva
A and
Câmara
NO
(2013). DEFICIENCY OF IL-10/IL-12 CYTOKINES EXACERBATE SYSTEMIC INFLAMMATORY RESPONSES IN RENAL INJURIES INDUCED BY ISCHEMIA AND REPERFUSION.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00494
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Received:
16 Apr 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Vanessa N Paiva, University of Bonn, Institute Reconstructive Neurobiology, Life&Brain center, Bonn, Germany, nunesp@uni-bonn.de