Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice

Hiroya Tanaka, Ting Sun, Hiroshi Kinashi, Keisuke Kamiya, Makoto Yamaguchi, Hironobu Nobata, Fumiko Sakata, Hangsoo Kim, Masashi Mizuno, Shunnosuke Kunoki, Yukinao Sakai, Akiyoshi Hirayama, Tomoyoshi Soga, Kazuhiro Yoshikawa, Takuji Ishimoto, Yasuhiko Ito

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Cardiovascular disease is the most common comorbidity in patients with chronic kidney disease (CKD), affecting both their prognosis and quality of life. Cardiac fibrosis is common in patients with CKD with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein-1, tumor necrosis factor-a, IL-1b, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) compared with Nx-salt mice treated with control rat rat IgG1 (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites, including histidine and c-butyrobetaine, were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, antifibrotic, and partial antioxidative effects in the heart of Nx-salt mice.

Original languageEnglish
Pages (from-to)F654-F665
JournalAmerican Journal of Physiology - Renal Physiology
Volume323
Issue number6
DOIs
Publication statusPublished - 2022 Dec

Keywords

  • cardiac fibrosis
  • cardiac inflammation
  • interleukin-6
  • salt loading
  • subtotal nephrectomized mice

ASJC Scopus subject areas

  • Physiology
  • Urology

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