Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis

Cheng Chi Chao, Shi Juan Chen, Iannis Adamopoulos, Nicole Davis, Kyu Hong, Anna Vu, Sylvia Kwan, Laurence Fayadat-Dilman, Agelio Asio, Edward P. Bowman

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine secreted by a subset of memory T cells and other innate immune cells. It is associated with rheumatoid arthritis (RA) due to IL-17A expression in RA synovial fluid. The severe bone erosive rat adjuvant-induced arthritis (rAIA) and mouse collagen-induced arthritis (mCIA) models were used to address the therapeutic efficacy of anti-IL-17A treatment with a focused investigation on bone protection. In the rAIA model, treatment with anti-IL-17A completely alleviated arthritis, lowered the level of receptor activator of NFκB ligand (RANKL), and inhibited structural damage to the bones. In the mCIA model, IL-17A neutralization coincident with arthritis development or in mice with established arthritis diminished joint swelling by inhibiting disease initiation and progression. Intriguingly, even the few joints that became outwardly severely inflamed in the presence of an anti-IL-17A antagonist had diminished joint histopathology scores compared to severely inflamed, control-treated mice. The bone-preserving property correlated with decreased RANKL message in severely inflamed paws of arthritic mice. These data identify IL-17A as a key factor in inflammation-mediated bone destruction and support anti-IL-17A therapy for the treatment of inflammatory bone diseases such as RA.

Original languageEnglish (US)
Pages (from-to)243-252
Number of pages10
JournalAutoimmunity
Volume44
Issue number3
DOIs
StatePublished - May 2011
Externally publishedYes

Keywords

  • adjuvant-induced arthritis
  • collagen-induced arthritis
  • IL-17A
  • inflammation
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chao, C. C., Chen, S. J., Adamopoulos, I., Davis, N., Hong, K., Vu, A., Kwan, S., Fayadat-Dilman, L., Asio, A., & Bowman, E. P. (2011). Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity, 44(3), 243-252. https://doi.org/10.3109/08916934.2010.517815