Decreased renal ischemia-reperfusion injury by IL-16 inactivation.
T-cell-mediated renal injury is a major cause of kidney transplant rejection and renal failure; hence, understanding T-cell migration within the kidney is important for preventing renal injury. Interleukin (IL)-16 is a T-cell chemoattractant produced by leukocytes. Here we measured IL-16 expression in the kidney and its role in renal ischemia-reperfusion injury induced by different conditions in several strains of mice. IL-16 was strongly expressed in distal and proximal straight tubules of the kidney. The IL-16 precursor protein was cleaved to a chemotactic form in cultured tubular epithelial cells. Inactivation of IL-16 by antibody therapy or IL-16 deficiency prevented ischemia-reperfusion injury as shown by reduced levels of serum creatinine or blood urea nitrogen compared to control mice. Further studies indicated that fewer CD4-cells infiltrated the post-ischemic kidneys of IL-16-deficient mice and that the protective effect of IL-16 antibody treatment was lymphocyte-dependent. Our results suggest that IL-16 is a critical factor in the development of inflammation-mediated renal injury and may be a therapeutic target for prevention of ischemia-reperfusion injury of the kidney.
Wang
S
S
Department of Medicine, The University of Western Ontario, London, Ontario, Canada.
Diao
H
H
Guan
Q
Q
Cruikshank
W W
WW
Delovitch
T L
TL
Jevnikar
A M
AM
Du
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D019410:Interleukin-16 / Q000276:immunology / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D019410:Interleukin-16; D012333:RNA, Messenger