Paper of the Month

January 2019

Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis, Journal of Experimental Medicine, DZHK authors: Weckbach, Grabmaier, Massberg

Myocarditis denotes an inflammatory response against the heart muscle, which is commonly triggered by cardiotropic viruses. Although myocarditis resolves completely without any treatment in the majority of patients, cardiac inflammation can become chronic and may ultimately lead to heart failure. DZHK scientists and researchers of the Collaborative Research Center 914 (Trafficking of Immune Cells in Inflammation, Development and Disease) elucidated the role of the cytokine midkine for the development and progression of myocarditis in a new study which is reported in the Journal of Experimental Medicine.

The authors analyzed tissue samples from patients with myocarditis. The researchers identified, for the first time, the presence of ‘neutrophil extracellular traps’ (NETs) in human cardiac tissue. NETs are formed when neutrophils are stimulated by viruses, bacteria or cytokines and thereby eject their DNA decorated with antimicrobial proteins serving as immune defense mechanism against pathogenic microorganisms. However, NETs can sustain chronic inflammation under sterile conditions and cause severe tissue injury. Targeting NETs indeed substantially reduced cardiac inflammation in a myocarditis mouse model in this study. The authors showed that midkine was able to mediate the formation of NETs and promoted the infiltration of neutrophils into the inflamed cardiac tissue in this model. Antibody-mediated inhibition of midkine led to a significant improvement in heart function and protected the tissue from undergoing fibrotic remodeling, a process which is a major contributor to heart failure.Therefore, blocking midkine or NETs could potentially represent novel and promising therapeutic options for patients with myocarditis.