AUTHOR=Zhang Yaozhong , Yang Qingqing , Peng Qi , Tian Zhihua , Lv Fen , Zeng Xiaomei , Jiang Zaixue , Cheng Qingqiu , Yang Lijun , Zhong Baimao , Lu Xiaomei , Zhu Yinghua TITLE=Impaired arginine/ornithine metabolism drives severe HFMD by promoting cytokine storm JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1407035 DOI=10.3389/fimmu.2024.1407035 ISSN=1664-3224 ABSTRACT=Introduction

The Hand, Foot and Mouth Disease (HFMD), caused by enterovirus 71 infection, is a global public health emergency. Severe HFMD poses a significant threat to the life and well-being of children. Numerous studies have indicated that the occurrence of severe HFMD is associated with cytokine storm. However, the precise molecular mechanism underlying cytokine storm development remains elusive, and there are currently no safe and effective treatments available for severe HFMD in children.

Methods

In this study, we established a mouse model of severe HFMD to investigate the molecular mechanisms driving cytokine storm. We specifically analyzed metabolic disturbances, focusing on arginine/ornithine metabolism, and assessed the potential therapeutic effects of spermine, an ornithine metabolite.

Results

Our results identified disturbances in arginine/ornithine metabolism as a pivotal factor driving cytokine storm onset in severe HFMD cases. Additionally, we discovered that spermine effectively mitigated the inflammatory injury phenotype observed in mice with severe HFMD.

Discussion

In conclusion, our findings provide novel insights into the molecular mechanisms underlying severe HFMD from a metabolic perspective while offering a promising new strategy for its safe and effective treatment.