Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction

Autor: Nur Hayati Jasmin, Angela Richard-Loendt, Kevin J. Woollard, Daniel J. Stuckey, Ana Garcia Diaz, Valerie Taylor Cummings, Mark F. Lythgoe, Tabitha Turner-Stokes, Marc J. George, Aroon D. Hingorani, Derek W. Gilroy, Francesca Launchbury
Rok vydání: 2020
Předmět:
0301 basic medicine
Cardiac function curve
CXCL
C-X-C motif ligand

Trop-T
troponin T

RCAEC
rat coronary artery endothelial cell

CCL
C-C motif chemokine ligand

Inflammation
030204 cardiovascular system & hematology
Pharmacology
Ab
antibody

sIL-6R
soluble IL-6 receptor

03 medical and health sciences
0302 clinical medicine
CMR
cardiac magnetic resonance

LVEF
left ventricular ejection fraction

MHC
major histocompatibility complex

Diseases of the circulatory (Cardiovascular) system
Medicine
STEMI
ST-segment-elevation MI

Myocardial infarction
Interleukin 6
1102 Cardiorespiratory Medicine and Haematology
ICAM-1
intercellular adhesion molecule 1

biology
business.industry
interleukin-6
TCZ
tocilizumab

Interleukin
1103 Clinical Sciences
medicine.disease
Fusion protein
IL
interleukin

NSTEMI
non–ST-segment-elevation MI

reperfusion
Blockade
c-caspase-3
cleaved caspase-3

myocardial infarction
030104 developmental biology
inflammation
RC666-701
MI
myocardial infarction

biology.protein
IS
infarct size

LGE
late-gadolinium enhancement

AAR
area at risk

Signal transduction
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Zdroj: JACC: Basic to Translational Science, Vol 6, Iss 5, Pp 431-443 (2021)
ISSN: 2452-302X
Popis: 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.
Databáze: OpenAIRE