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.