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Managing Macrophages in Rheumatoid Arthritis by Reform or Removal

  • RHEUMATOID ARTHRITIS (LW MORELAND, SECTION EDITOR)
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Abstract

Macrophages play a central role in the pathogenesis of rheumatoid arthritis (RA). There is an imbalance of inflammatory and antiinflammatory macrophages in RA synovium. Although the polarization and heterogeneity of macrophages in RA have not been fully uncovered, the identity of macrophages in RA can potentially be defined by their products, including the co-stimulatory molecules, scavenger receptors, different cytokines/chemokines and receptors, and transcription factors. In the last decade, efforts to understand the polarization, apoptosis regulation, and novel signaling pathways in macrophages, as well as how distinct activated macrophages influence disease progression, have led to strategies that target macrophages with varied specificity and selectivity. Major targets that are related to macrophage development and apoptosis include TNF-α, IL-1, IL-6, GM-CSF, M-CSF, death receptor 5 (DR5), Fas, and others, as listed in Table 1. Combined data from clinical, preclinical, and animal studies of inhibitors of these targets have provided valuable insights into their roles in the disease progression and, subsequently, have led to the evolving therapeutic paradigms in RA. In this review, we propose that reestablishment of macrophage equilibrium by inhibiting the development of, and/or eliminating, the proinflammatory macrophages will be an effective therapeutic approach for RA and other autoimmune diseases.

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Disclosure

Funding for this research was made possible by the American College of Rheumatology (ACR) Research and Education Foundation and the Lupus Research Institute (LRI). Dr. Li has received grant support (Fellowship Award) from the Arthritis Foundation. Dr. Hsu has received grant support from the LRI and NIH 1 R01 AI083705. Dr. Mountz has received grant support from the ACR, NIH RO1 AI071110-01A1, VA 1I01BX000600, and Daiichi-Sankyo Co Ltd.

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Authors and Affiliations

  1. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, SHEL Bldg., Suite 337, 1825 University Blvd., Birmingham, AL, 35294-2182, USA

    Jun Li

  2. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, SHEL Bldg., Suite 311, 1825 University Blvd., Birmingham, AL, 35294-2182, USA

    Hui-Chen Hsu

  3. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, SHEL Bldg., Suite 307, 1825 University Blvd., Birmingham, AL, 35294-2182, USA

    John D. Mountz

  4. Department of Medicine, Birmingham VA Medical Center, Birmingham, AL, 35233, USA

    Hui-Chen Hsu & John D. Mountz

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  1. Jun Li
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  2. Hui-Chen Hsu
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Correspondence to John D. Mountz.

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Li, J., Hsu, HC. & Mountz, J.D. Managing Macrophages in Rheumatoid Arthritis by Reform or Removal. Curr Rheumatol Rep 14, 445–454 (2012). https://doi.org/10.1007/s11926-012-0272-4

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