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GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica

William F Jiemy1, Anqi Zhang1, Wayel H Abdulahad2

  • 1Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Annals of the Rheumatic Diseases
|February 6, 2025
PubMed
Abstract

Insights

Polymyalgia rheumatica (PMR) involves expanded and activated monocytes. Macrophages in affected tissues produce key inflammatory cytokines like IL-6, suggesting they are crucial therapeutic targets for PMR.

Area of Science:

  • Immunology
  • Rheumatology

Background:

  • Limited understanding of polymyalgia rheumatica (PMR) immunopathology, with peripheral blood studies suggesting macrophages are key players.
  • Investigating the factors driving pro-inflammatory macrophage development and function in PMR.

Purpose of the Study:

  • To identify factors driving pro-inflammatory macrophage development in PMR.
  • To elucidate the functional role of macrophages in PMR immunopathology.

Main Methods:

  • Flow cytometry to analyze monocyte phenotypes in peripheral blood and bursal fluid.
  • Immunohistochemistry and immunofluorescence to characterize macrophages in affected tissues.
  • In vitro macrophage differentiation cultures to assess cytokine functions.

Main Results:

  • Increased and activated monocytes (CD14highCD16- and CD14highCD16+) observed in PMR patients.
  • Macrophages dominated immune infiltrates in PMR tissue, expressing abundant pro-inflammatory cytokines, notably IL-6.
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly elevated in PMR tissue, driving IL-6 production.

Conclusions:

  • The monocyte compartment is expanded and activated in PMR.
  • Macrophages in PMR-affected tissues are significant producers of pro-inflammatory cytokines like IL-6.
  • A cytokine network involving GM-CSF, M-CSF, and IFN-γ likely drives macrophage pro-inflammatory functions, identifying macrophages as potential therapeutic targets for PMR.

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