Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction
oleh: Marc Jonathan George, MB ChB, PhD, Nur Hayati Jasmin, BSc, MRes, Valerie Taylor Cummings, Angela Richard-Loendt, BSc, MSc, Francesca Launchbury, BSc, Kevin Woollard, PhD, Tabitha Turner-Stokes, MB BChir, Ana Isabel Garcia Diaz, BSc, Mark Lythgoe, PhD, Daniel James Stuckey, BSc, DPhil, Aroon Dinesh Hingorani, MB BS, PhD, Derek William Gilroy, PhD
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2021-05-01 |
Deskripsi
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.