Inflammatory Responses in Pediatric Patients with Suspected Myocarditis

Abstract

Myocarditis is one major cause for the development of acute or chronic heart failure where immunosuppressive therapies are still divergently discussed. The aim of this study was to analyze cytokines in children with suspected myocarditis to describe their immunologic patterns and to reveal potential therapeutic targets. Sera of children hospitalized with suspected myocarditis and sera from a pediatric control cohort collected during April 2017 and July 2019 were analyzed. Sera were taken after admission and before further intensive care treatment. The cytokines Interleukin (IL)-1 beta, IL-2, IL-6, IL-10 and IL-1 receptor antagonist (IL-1RA) were analyzed by enzyme-linked immunosorbent assay (ELISA) kits of Meso Scale Discovery Inc. and R&D Systems™. A subcohort of patients with a severe disease course needing mechanical circulatory support, heart transplantation or death was defined. Thirty-nine children with suspected myocarditis, median age (IQR) 12.3 (2.1-16.4) years, 55% male and 33 controls 5.3 (3.4-9.3) years, 31% male were included in the analyses. IL-1RA was significantly higher in patients (671.2 pg/ml) than in controls (379.0 pg/ml; p<0.001). Also IL-6 was significantly higher in patients compared to controls (3.4 pg/ml vs. 0.5 pg/ml; p<0.001). Within the patient cohort IL-1RA correlated positively with leucocytes (rs=0.432, p=0.017). IL-6 correlated with leucocytes (rs=0.393, p=0.032), CRP (rs=0.356, p=0.050), Troponin (rs=0.502, p=0.015). IL-2 and IL-10 correlated with BNP (IL-2: rs=0.481, p=0.011, IL-10: rs=0.387, p=0.046) and the Z-Score of the left ventricular enddiastolic diameter in echocardiography (IL-2: rs=0.625, p<0.001, IL-10: rs=0.394, p=0.028). Within the subcohort with severe disease courses (n=9), IL-1ß was not significantly reduced compared to the other patients and the controls (p=0.387) with a corresponding significantly elevated IL1-RA and IL-6 (p<0.001, respectively). In children with suspected myocarditis cytokines as IL-2, IL-6 and IL-10 correlate with myocardial damage and dysfunction as potential markers for heart failure. The higher levels of IL-1RA in children with severe disease course may represent the immunologic reaction of a more fulminant myocarditis pointing towards potential therapeutic targets in children with an inappropriate elevation of IL-1RA.