Persistent renal and extrarenal immune changes after severe ischemic injury.
BACKGROUND
Renal ischemia/reperfusion (I/R) injury is associated with delayed graft function and decreased long-term allograft function. However, most experimental studies evaluating renal I/R injury have focused on acute events after ischemia. T cells are potential candidates to link preservation injury, alloimmunity, and fibrosis. We hypothesized that severe renal I/R injury would generate long-term kidney damage and immune changes.


METHODS
C57BL/6 mice underwent 60 minutes of warm unilateral I/R injury or sham surgery and were studied for 6 weeks. Serum creatinine, renal histology, and albumin excretion were measured. Phagocyte infiltration, CD4+ infiltration, renal cytokine expression, and splenic lymphocyte intracellular cytokine production were also measured in mice at 6 weeks.


RESULTS
Serum creatinine levels rose following 60 minutes of unilateral I/R injury compared to sham mice. Histologic analysis of ischemic kidneys at 6 weeks revealed a pronounced loss of tubular architecture and infiltration of inflammatory cells. Phagocyte and CD4+ T-cell infiltration were significantly increased in ischemic kidneys. This was accompanied by a significant increase in interleukin (IL)-1beta and regulated upon activation, normal T-cell expressed and secreted (RANTES) expression. Despite similar splenic CD4 and CD8 numbers, intracellular cytokine staining of T cells revealed a significant increase in interferon-gamma (IFN-gamma) in I/R injury mice compared to sham mice.


CONCLUSIONS
Persistent renal and extrarenal immune responses occur after a single episode of severe I/R injury. These immune processes resulting from injury could in turn have long-term consequences on progression of renal disease in transplanted and native kidneys.
Burne-Taney
Melissa J
MJ
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. mburne1@jhmi.edu
Yokota
Naoko
N
Rabb
Hamid
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018946:Chemokine CCL5 / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000502:physiology; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology
D018946:Chemokine CCL5; D007375:Interleukin-1; D007371:Interferon-gamma