IL-18 contributes to renal damage after ischemia-reperfusion

Huiling Wu, Melissa L. Craft, Peng Wang, Kate R. Wyburn, Gang Chen, Jin Ma, Brett Hambly, Steven J. Chadban

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

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 reno-protective 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.

Original languageEnglish
Pages (from-to)2331-2341
Number of pages11
JournalJournal of the American Society of Nephrology : JASN
Volume19
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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