The protective role of interleukin-18 binding protein in a murine model of cardiac ischemia/reperfusion injury.
IL-18, a proinflammatory cytokine, is produced by macrophages, epithelial cells, T cells, neutrophils, NK-T cells, and B cells, and has been implicated in the pathophysiology of a variety of inflammatory diseases including ischemia/reperfusion (IR) injury, transplant rejection, and autoimmune disease. Recent study indicated that neutralization of IL-18 with anti-IL-18 antibody or IL-18-binding protein (IL-18BP) ameliorates IR-induced myocardial injury. However, the mechanism needs to be further investigated. In our current study, syngeneic heterotopic heart transplantation was performed by a modified non-suture cuff technique. We found that IL-18BP treatment ameliorated cardiomyocyte necrosis and infiltration of CD4(+) T cells, neutrophils, and macrophages. IL-18BP-treated mice exhibited decreased expression of inflammatory cytokines including IL-1β, IL-23, IL-18, and IL-17. IL-18BP treatment suppressed Th17 differentiation in vivo and in vitro. Adoptive transfer of T cells from IL-18BP-treated mice showed alleviated cardiac IR injury when compared with that transferred from control mice. Furthermore, the decreased infiltration of mononuclear cells and production of troponin T (TnT) induced by IL-18BP treatment were both abrogated by additional administration of recombinant mouse IL-17 (rmIL-17). These data revealed a protective role of IL-18BP in cardiac IR injury. Above all, IL-18BP ameliorates cardiac IR injury in part through suppression of Th17 differentiation.
Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Haifeng
H
Gu
Department of Geriatrics, The An Kang Hospital of Hangzhou Police, Hangzhou, China.
Minghua
M
Xie
Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Liqian
L
Xu
Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Xiaojun
X
Zheng
Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Yunmei
Y
Yang
Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Xueying
X
Lv
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000009:adverse effects; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D064596:Isografts; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C118370:interleukin-18 binding protein
IL-17; IL-18-binding protein; Th17 cells; cardiac ischemia/reperfusion injury