Potential therapeutic targets of fibrosis in inflammatory rheumatic diseases

Best Pract Res Clin Rheumatol. 2024 May;38(2):101945. doi: 10.1016/j.berh.2024.101945. Epub 2024 Apr 15.

Abstract

Fibrosis is commonly associated with chronic rheumatic diseases, and causes substantial morbidity and mortality. Treatment of fibrosis is extremely challenging but is badly needed, as approved antifibrotic therapies fibrosis do not halt its progression, which will be discussed with a focus on pulmonary fibrosis. Findings from recent studies indicate several therapeutic targets for treating fibrosis. Interleukin-11 is emerging as a fibrogenic cytokine whose activity can be blocked with neutralizing monoclonal antibodies. Fibroblast activation protein (FAP) is highly expressed by activated fibroblasts in inflammatory and fibrotic tissues. Targeting FAP with different modalities has been extensively explored as adjunct treatment for cancer, which can also apply to treating fibrosis in rheumatic diseases.

Keywords: Fibroblast; Fibroblast activation protein; Fibrosis; Idiopathic pulmonary fibrosis; Interleukin-11; Interstitial lung disease.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endopeptidases
  • Fibrosis
  • Gelatinases / antagonists & inhibitors
  • Gelatinases / metabolism
  • Humans
  • Interleukin-11 / metabolism
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Pulmonary Fibrosis / drug therapy
  • Pulmonary Fibrosis / etiology
  • Rheumatic Diseases* / drug therapy
  • Rheumatic Diseases* / immunology
  • Serine Endopeptidases / metabolism

Substances

  • fibroblast activation protein alpha
  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • Interleukin-11
  • Gelatinases