Evaluation of therapeutic potential of ivermectin against complete Freund's adjuvant-induced arthritis in rats: Involvement of inflammatory mediators

Fundam Clin Pharmacol. 2023 Oct;37(5):971-982. doi: 10.1111/fcp.12902. Epub 2023 May 7.

Abstract

Rheumatoid arthritis is a chronic systemic inflammatory disease with genetic manifestations. According to recently published case reports, patients taking corticosteroid medication for the management of rheumatoid arthritis develop strongloidiasis and are at high risk of developing associated infections. This study explored the antiarthritic role of ivermectin, a drug used in the treatment of strongyloides and to compare its results with dexamethasone. Thirty-two male Wistar rats were randomly divided into four groups: control, diseased, dexamethasone, and ivermectin groups. Rheumatoid arthritis in all rats except the control group was induced by using complete Freund's adjuvant. After 7 days of rheumatoid arthritis induction, animals were treated with dexamethasone 5 mg/kg and ivermectin 6 mg/kg. Body weight, visual arthritic score, total leukocyte count, differential leukocyte count, proinflammatory genes, and histopathological findings were used to assess the effects of ivermectin on rheumatoid arthritis. Treatment with ivermectin showed a significant reduction in inflammatory cells levels, body weight, and visual arthritic score, indicating an improvement in the degree of inflammation as compared with the diseased group. Treatment with ivermectin and dexamethasone significantly reduced the augmentation in the mRNA expression levels of IL-17, TLR-2, TNF, and NF-κB as a result of arthritic development. Ivermectin treatment also showed a significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to dexamethasone, a corticosteroid used for the treatment of rheumatoid arthritis. Ivermectin has significant antiarthritic properties and can be a novel treatment agent for the management of rheumatoid arthritis patients suffering from strongyloidiasis.

Keywords: dexamethasone; ivermectin; rheumatoid arthritis; strongyloidiasis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Experimental* / chemically induced
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Rheumatoid* / drug therapy
  • Body Weight
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Freund's Adjuvant / adverse effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation Mediators
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use
  • Male
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Freund's Adjuvant
  • Ivermectin
  • Plant Extracts
  • Inflammation Mediators
  • Anti-Inflammatory Agents
  • Dexamethasone