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.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose
Article highlights
Sarcoidosis etiology is unclear at this point, but likely due to polygenic mechanisms and maladapted host’s immune response to common environmental exposures resulting in highly variable clinical phenotypes.
Current therapy primarily targets M1/Th1 inflammatory pathway, but M2/Th2 inhibitory agents could potentially be beneficial in preventing fibrosis and lethal complications.
Sarcoidosis treatment might require restoration of a healthy balance of inflammatory and regulatory pathways by modulating both M1/M2 instead of targeting one over the other.
Lack of reliable research models for sarcoidosis hinders progress towards elucidating disease mechanisms and establishing novel therapies.
Collaboration among sarcoidosis centers with commitment to develop highly standardized and reproducible scientific techniques to accelerate scientific discovery and to promote effective clinical trials.
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