The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure

Najah Harouki; Lionel Nicol; Isabelle Remy-Jouet; Jean-Paul Henry; Anais Dumesnil; Annie Lejeune; Sylvanie Renet; Francesca Golding; Zoubir Djerada; Didier Wecker; Virginie Bolduc; Muriel Bouly; Jerome Roussel; Vincent Richard; Paul Mulder

doi:10.1016/j.jacbts.2017.06.005

The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure

JACC Basic Transl Sci. 2017 Aug 28;2(4):418-430. doi: 10.1016/j.jacbts.2017.06.005. eCollection 2017 Aug.

Authors

Najah Harouki^{1

2

3}, Lionel Nicol^{1

2

3

4}, Isabelle Remy-Jouet^{1

2

3}, Jean-Paul Henry^{1

2

3}, Anais Dumesnil^{1

2

3}, Annie Lejeune^{1

2

3}, Sylvanie Renet^{1

2

3}, Francesca Golding^{1

2

3}, Zoubir Djerada^{1

2

3

5}, Didier Wecker⁶, Virginie Bolduc⁷, Muriel Bouly⁷, Jerome Roussel⁷, Vincent Richard^{1

2

3}, Paul Mulder^{1

2

3

4}

Affiliations

¹ INSERM U1096, Rouen, France.
² Normandy University, IRIB, Rouen, France.
³ Unité de formation et de recherche de Médecine et Pharmacie, Rouen University, Rouen, France.
⁴ Plateau d'Imagerie CardioThoracique de l'Université de Rouen, Rouen, France.
⁵ Pharmacology Department, Centre Hospitalier Universitaire de Reims, Reims, France.
⁶ Bruker Biospin MRI GMBH, Ettlingen, Germany.
⁷ Institut de Recherches Internationales Servier, Suresnes, France.

Abstract

This study reports preclinical data showing that the interleukin (IL)-1β modulation is a new promising target in the pathophysiological context of heart failure. Indeed, in nondiabetic Wistar and diabetic Goto-Kakizaki rats with chronic heart failure induced by myocardial infarction, administration of the IL-1β antibody gevokizumab improves 'surrogate' markers of survival (i.e., left ventricular remodeling, hemodynamics, and function as well as coronary function). However, whether IL-1β modulation per se or in combination with standard treatments of heart failure improves long-term outcome in human heart failure remains to be determined.

Keywords: GK, Goto-Kakisaki; I/R, ischemia/reperfusion; IL, interleukin; IL-1β; LV, left ventricle/ventricular; LVEDP, left ventricular end-diastolic pressure; LVEDPV, left ventricular end-diastolic pressure–volume relationship; LVESP, left ventricular end-systolic pressure; LVESPVR, left ventricular end-systolic pressure–volume relationship; ROS, reactive oxygen species; SOD, superoxide dismutase; cardiovascular function; heart failure; ischemia/reperfusion.