Selective interleukin-6 trans-signaling blockade is more effective than panantagonism in reperfused myocardial infarction
MJ George, NH Jasmin, VT Cummings… - Basic to Translational …, 2021 - jacc.org
MJ George, NH Jasmin, VT Cummings, A Richard-Loendt, F Launchbury, K Woollard…
Basic to Translational Science, 2021•jacc.orgSummary Interleukin (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 …
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 …
Summary
Interleukin (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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