George, MJ;
Jasmin, NH;
Cummings, VT;
Richard-Loendt, A;
Launchbury, F;
Woollard, K;
Turner-Stokes, T;
... Gilroy, DW; + view all
(2021)
Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction.
JACC: Basic to Translational Science
10.1016/j.jacbts.2021.01.013.
(In press).
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Abstract
Interleukin-6 (IL-6) is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti–IL-6 antibodies (Abs) result in panantagonism. In a rat model of reperfused MI, sgp130Fc, but not anti–IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI. These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI.
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