IL-18 Contributes to Renal Damage after Ischemia-Reperfusion

[摘要] IL-18 is a proinflammatory cytokine produced by macrophages and other cell types present in the kidney during ischemia-reperfusion injury (IRI), but its role in this injury is unknown. Here, compared with wild-type mice, IL-18−/− mice subjected to kidney IRI demonstrated better kidney function, less tubular damage, reduced accumulation of neutrophils and macrophages, and decreased expression of proinflammatory molecules that are downstream of IL-18. For determination of the relative contributions of leukocytes and parenchymal cells to IL-18 production and subsequent kidney damage during IRI, bone marrow–chimeric mice were generated. Wild-type mice engrafted with IL-18−/− hemopoietic cells showed less kidney dysfunction and tubular damage than IL-18−/− mice engrafted with wild-type bone marrow. In vitro, macrophages produced IL-18 mRNA and protein in response to ischemia. These data suggest bone marrow–derived cells are the key contributors to IL-18–mediated effects of renal IRI. Finally, similar to IL-18−/− mice, pretreatment of wild-type mice with IL-18–binding protein was renoprotective in this model of IRI. In conclusion, IL-18, derived primarily from cells of bone marrow origin, contributes to the renal damage observed during IRI. IL-18–binding protein may have potential as a renoprotective therapy.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome