Potential immunotherapies for sarcoidosis

Expert Opin Biol Ther. 2018 Apr;18(4):399-407. doi: 10.1080/14712598.2018.1427727. Epub 2018 Jan 17.

Abstract

Introduction: Sarcoidosis is a chronic granulomatous inflammatory disease that commonly causes lung disease, but can affect other vital organs and tissues. The cause of sarcoidosis is unknown, and current therapies are commonly limited by lack of efficacy, adverse side effects, and excessive cost.

Areas covered: The manuscript will provide a review of current concepts relating to the pathogenesis of sarcoidosis, and how these disease mechanisms may be leveraged to develop more effective treatments for sarcoidosis. It provides only a brief summary of currently accepted therapy, while focusing more extensively on potential novel therapies.

Expert opinion: Current sarcoidosis therapeutic agents primarily target the M1 or pro-inflammatory pathways. Agents that prevent M2 polarization, a regulatory phenotype favoring fibrosis, are attractive treatment alternatives that could potentially prevent fibrosis and associated life threatening complications. Effective treatment of sarcoidosis potentially requires simultaneous modulation both M1/M2 polarization instead of suppressing one pathway over the other to restore immune competent and inactive (M0) macrophages.

Keywords: Sarcoidosis; fibrosis; immunotherapy; inflammation; macrophage; mechanism; therapeutic; treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Granuloma / metabolism
  • Granuloma / prevention & control
  • Humans
  • Immunotherapy*
  • Leflunomide / pharmacology
  • Leflunomide / therapeutic use
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Rituximab / therapeutic use
  • Sarcoidosis / metabolism
  • Sarcoidosis / pathology
  • Sarcoidosis / therapy*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal, Humanized
  • Rituximab
  • fontolizumab
  • Leflunomide