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Analysis of Cytokine Profiles in Pediatric Myocarditis Multicenter Study

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Abstract

Acute myocarditis (AM) is an inflammatory disease of the heart muscle that can progress to fulminant myocarditis (FM), a severe and life-threatening condition. The cytokine profile of myocarditis in children, especially in relation to fulminant myocarditis, is not well understood. This study aims to evaluate the cytokine profiles of acute and fulminant myocarditis in children. Pediatric patients diagnosed with myocarditis were included in the study. Cytokine levels were measured using a multiplexed fluorescent bead-based immunoassay. Statistical analysis was performed to compare patient characteristics and cytokine levels between FM, AM, and healthy control (HC) groups. Principal component analysis (PCA) was applied to cytokine groups that were independent among the FM, AM, and HC groups. The study included 22 patients with FM and 14 with AM patients. We identified four cytokines that were significantly higher in the FM group compared to the AM group: IL1-RA (p = 0.002), IL-8 (p = 0.005), IL-10 (p = 0.011), and IL-15 (p = 0.005). IL-4 was significantly higher in the AM group compared to FM and HC groups (p = 0.006 and 0.0015). PDGF-AA, and VEGF-A were significantly lower in the FM group than in the AM group (p = 0.013 and <0.001). Similar results were obtained in PCA. Cytokine profiles might be used to differentiate pediatric FM from AM, stratify severity, and predict prognosis. The targeted therapy that works individual cytokines might provide a potential treatment for reducing the onset of the FM and calming the condition, and further studies are needed.

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Acknowledgements

We would like to express our sincere gratitude to Naoko Takahashi at the Aichi Children’s Health and Medical Center for her invaluable assistance with specimen collection, to Akiko Yoshikawa at Fujita Health University School of Medicine for her support with experimental techniques, to Toshiya Kokaji at the Nara Institute of Science and Technology for his helpful and technical comments on statistical analysis, and to Aamir Jeewa at the Hospital for Sick Children for reviewing the content and providing expertise in English literature.

Funding

This research was supported by grants from the Suzuken Memorial Foundation 2021, Japan.

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Author notes

  1. Yoji Nomura and Takanori Suzuki have contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Cardiology, Aichi Children’s Health and Medical Center, Aichi, Japan

    Yoji Nomura, Takanori Suzuki, Ryoichi Ito, Yasunori Oshima, Machiko Kito, Yuki Imai, Satoru Kawai & Kazushi Yasuda

  2. Department of Pediatrics, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake cho, Toyoake, Aichi, 470-1192, Japan

    Takanori Suzuki, Hidetoshi Uchida, Kei Kozawa, Kazuyoshi Saito, Tadayoshi Hata & Tetsushi Yoshikawa

  3. Department of Computational Biology, Fujita Health University School of Medicine, Aichi, Japan

    Katsuyuki Kunida

  4. Department of Biomedical Data Science, Fujita Health University School of Medicine, Aichi, Japan

    Junichiro Yoshimoto

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  1. Yoji Nomura
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Contributions

YN and TS wrote the first draft of the manuscript. KY conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. KK, HU, RI, YO, MK, YI, SK, KK, KS, TH, JY, and TY, conceptualized and designed the study, and coordinated and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

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Correspondence to Takanori Suzuki.

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Nomura, Y., Suzuki, T., Kunida, K. et al. Analysis of Cytokine Profiles in Pediatric Myocarditis Multicenter Study. Pediatr Cardiol (2024). https://doi.org/10.1007/s00246-024-03452-6

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