Therapeutic effect of imiquimod on dextran sulfate sodium-induced ulcerative colitis in mice

PLoS One. 2017 Oct 19;12(10):e0186138. doi: 10.1371/journal.pone.0186138. eCollection 2017.

Abstract

Background: Imiquimod is a Toll-like receptor-7 agonist that regulates immunity and can be used as an immune adjuvant. Ulcerative colitis has a close correlation with immune disorder.

Aim: To investigate the therapeutic effect of imiquimod on dextran sulfate sodium (DSS)-induced colitis and explore the underlying mechanisms.

Methods: C57BL/6J C57 mice received 3% DSS for 7 days to induce ulcerative colitis. Groups of mice were intraperitoneally injected with dexamethasone (DXM, 1.5 mg/kg) or imiquimod (IMQ, 30 mg/kg) at the same time daily. During the experimental period, clinical signs, body weight, stool consistency and visible fecal blood were monitored and recorded daily; colitis was evaluated by disease activity index (DAI) score and by histological score. At the conclusion of the experiment, the level of colonic myeloperoxidase (MPO) activity and the serum levels of the cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured.

Results: Administration of 3% DSS for 7 days successfully induced acute colitis associated with diarrhea, bloody mucopurulent stool, body weight decreases, and other changes. Colitis severity was significantly ameliorated in the IMQ treatment groups, as determined by hematoxylin-eosin (HE) staining and histopathological scores. Moreover, IMQ significantly reduced the activity of MPO in colonic tissue and the serum levels of inflammatory cytokines, increased colon length and spleen weight, and effectively inhibited microscopic damage to the colon tissue.

Conclusion: IMQ had beneficial effects on DSS-induced ulcerative colitis, supporting its further development and clinical application in ulcerative colitis.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Aminoquinolines / therapeutic use*
  • Animals
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colon / drug effects
  • Colon / enzymology
  • Colon / pathology
  • Cytokines / biosynthesis
  • Dextran Sulfate / adverse effects*
  • Imiquimod
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • Cytokines
  • Dextran Sulfate
  • Peroxidase
  • Imiquimod

Grants and funding

The authors received no specific funding for this work.