Recombinant Human Soluble Thrombomodulin Suppresses Arteritis in a Mouse Model of Kawasaki Disease

J Vasc Res. 2022;59(3):176-188. doi: 10.1159/000520717. Epub 2021 Dec 20.

Abstract

Introduction and objective: Kawasaki disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and primarily affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, which increases their risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulant, anti-inflammatory, and cytoprotective properties on the development of coronary arteritis in a mouse model of vasculitis.

Methods: An animal model of KD-like vasculitis was created by injecting mice with Candida albicans water-soluble fraction (CAWS). This model was used to investigate the mRNA expression of interleukin (IL)-10, tumour necrosis factor alpha (TNF-α), and tissue factor (TF), in addition to histopathology of heart tissues.

Results: rTM treatment significantly reduces cardiac vascular endothelium hypertrophy by 34 days after CAWS treatment. In addition, mRNA expression analysis revealed that rTM administration increased cardiac IL-10 expression until day 27, whereas expression of TNF-α was unaffected. Moreover, in the spleen, rTM treatment restores IL-10 and TF expression to normal levels.

Conclusion: These findings suggest that rTM suppresses CAWS-induced vasculitis by upregulating IL-10. Therefore, rTM may be an effective treatment for KD.

Keywords: Anti-inflammatory functions; Candida albicans water-soluble fraction; Kawasaki disease; Recombinant human soluble thrombomodulin; Vasculitis.

MeSH terms

  • Animals
  • Arteritis* / drug therapy
  • Arteritis* / pathology
  • Candida albicans / metabolism
  • Coronary Vessels / metabolism
  • Disease Models, Animal
  • Humans
  • Immunoglobulins, Intravenous
  • Interleukin-10
  • Mice
  • Mucocutaneous Lymph Node Syndrome* / drug therapy
  • RNA, Messenger
  • Recombinant Proteins / therapeutic use
  • Thrombomodulin* / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasculitis* / drug therapy
  • Vasculitis* / prevention & control

Substances

  • Immunoglobulins, Intravenous
  • RNA, Messenger
  • Recombinant Proteins
  • Thrombomodulin
  • Tumor Necrosis Factor-alpha
  • Interleukin-10