Reduced acute myocardial ischemia–reperfusion injury in IL-6-deficient mice employing a closed-chest model

Reduced acute myocardial ischemia–reperfusion injury in IL-6-deficient mice employing a closed-chest model

Jong, Willeke M.C. (Amsterdam UMC)
ten Cate, Hugo (Universiteit Maastricht)
Linnenbank, A.C. (TU Delft Bio-Electronics)
de Boer, Onno J. (Amsterdam UMC)
Reitsma, Pieter H. (Leiden University Medical Center)
de Winter, Robbert J. (Amsterdam UMC)
Zuurbier, Coert (Amsterdam UMC)

2016

Objective and design: We examined the role of IL-6 in the temporal development of cardiac ischemia–reperfusion injury employing a closed-chest I/R model. Materials/methods: Infarction, local and systemic inflammation, neutrophil infiltration, coagulation and ST elevation/resolution were compared between wild-type (WT) and IL-6-deficient (IL-6^−/−) mice after 1 h ischemia and 0, ½, 3, and 24 h reperfusion. Results: IL-6 deficiency reduced infarct size at 3 h reperfusion (28.8 ± 4.5 % WT vs 17.6 ± 2.5 % IL-6^−/−), which reduction persisted and remained similar at 24 h reperfusion (25.1 ± 3.0 % WT vs 14.6 ± 4.4 % IL-6^−/−). Serum Amyloid A was reduced at 24 h reperfusion only (57.5 ± 4.9 WT vs 24.8 ± 5.6 ug/ml IL-6^−/− mice). Cardiac cytokines (IL-6, IL-1β and TNFα) peaked at 3 h reperfusion, but IL-1β and TNFα levels were unaffected by IL-6 deficiency. Significant neutrophil influx was only detected at 24 h reperfusion and was similar for WT and IL-6^−/−. Tissue factor peaked at 24 h reperfusion, whereas fibrin/fibrinogen peaked at 3 h reperfusion and was completely resolved at 24 h reperfusion; both coagulation factors were unaltered by IL-6 deficiency. Prolonged ST elevation was observed during ischemia that completely resolved for both genotypes at early reperfusion. Conclusions: The data suggest that, in the absence of major surgical intervention, IL-6 contributes to the development of infarct size in the early phase of reperfusion; this contribution did not depend on neutrophil influx, IL-1β and TNFα, tissue factor and fibrin.

Closed-chest model
Heart
IL-6
Inflammation
Ischemia/reperfusion injury

http://resolver.tudelft.nl/uuid:580a2b41-0c38-49cc-b0af-7812ca143b82

https://doi.org/10.1007/s00011-016-0931-4

1023-3830

Inflammation Research, 65 (6), 489-499

Institutional Repository

journal article

© 2016 Willeke M.C. Jong, Hugo ten Cate, A.C. Linnenbank, Onno J. de Boer, Pieter H. Reitsma, Robbert J. de Winter, Coert Zuurbier