Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice

Mediators Inflamm. 2017:2017:5635929. doi: 10.1155/2017/5635929. Epub 2017 Nov 22.


Background: Interleukin- (IL-) 22 is considered a proinflammatory cytokine. Recent evidence has demonstrated that it plays a role in cardiovascular diseases. In the recent study, we investigate whether IL-22 is involved in cardiac hypertrophy.

Methods: Angiotensin II was used to build hypertrophy model and the IL-22 and IL-22 receptor 1 (IL-22R1) levels in heart tissue were measured. In addition, angiotensin II-treated mice received an injection of anti-IL-22-neutralizing antibody (nAb) to investigate the effects of IL-22 nAb on myocardial hypertrophy, cardiac function, and cardiac fibrosis; the activation of the signaling pathway and the prohypertrophic inflammatory cytokine mRNA levels was detected. Furthermore, the effect of IL-22 nAb on angiotensin II-induced hypertrophy in vitro was also determined.

Results: IL-22 and IL-22R1 levels were significantly increased after angiotensin II infusion. Anti-IL-22 nAb significantly alleviated the severity of hypertrophy, prevented systolic and diastolic abnormalities, reduced cardiac fibrosis, STAT3 and ERK phosphorylation, and downregulated the mRNA expression of IL-17, IL-6, IL-1β, IFN-γ, and TNF-α. In addition, IL-22 nAb attenuated angiotensin II-induced hypertrophy in H9C2 cells.

Conclusion: Our data demonstrated that neutralization of IL-22 alleviated angiotensin II-induced cardiac hypertrophy. The downregulation of IL-22 may be a novel therapeutic strategy to prevent cardiac hypertrophy.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Antibodies, Neutralizing / therapeutic use*
  • Cardiomegaly / drug therapy*
  • Cardiomegaly / etiology
  • Cardiomegaly / immunology
  • Cardiomegaly / metabolism
  • Cells, Cultured
  • Cytokines / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibrosis
  • Interleukin-22
  • Interleukins / antagonists & inhibitors*
  • Interleukins / immunology
  • Interleukins / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / pathology
  • RNA, Messenger / analysis
  • STAT3 Transcription Factor / metabolism


  • Antibodies, Neutralizing
  • Cytokines
  • Interleukins
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Angiotensin II
  • Extracellular Signal-Regulated MAP Kinases