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Table 4 Overview of pro-inflammatory interleukins relevant to macrophage (dys)function in rheumatoid arthritis

From: Cells of the synovium in rheumatoid arthritis. Macrophages

Family Cytokine Pro-inflammatory Dual Autocrine Main pathogenetic features
IL-1 IL-1 X - X Predominantly produced by Mφ
      Critical mediator of tissue damage
      Possesses autocrine features [43,51-53]
  IL-18 X - X Predominantly produced by Mφ
      Critical pleiotropic mediator of disease
      Possesses autocrine features [59-61]
  IL-33 X X - Produced by endothelial cells
      Important Th2-inducing component in allergy/autoimmunity
      Signals via IL-1 receptor-related protein (ST2)
      Nuclear factor with transcriptional repressor properties (≈ nuclear factor from high endothelial venules) [111-113]
IL-18 inducible IL-32 X - - Pro-inflammatory effects on both myeloid and non-myeloid cells [114,115]
IL-2 IL-7 X - - Elevated in RA, although a relative paucity is also possible [116,117]
      Induces osteoclastic bone loss in mice [118]
  IL-15 X - X Produced by Mφ
      Important autocrine mediator of disease processes [21,56-58]
  IL-21 X - - Only IL-21R is expressed by synovial Mφ and fibroblasts [119]
IL-6 IL-6 X X - Predominantly produced by fibroblasts under the influence of Mφ
      Most strikingly elevated cytokine in acute RA, with phase-dependent differential effects [17,75,76] (reviewed in [2,77])
  IL-31 X - - Induces experimental dermatitis [120]
  LIF X - - Stimulates proteoglycan resorption in cartilage [121]
  Oncostatin M X - - Recruits leukocytes to inflammatory sites and stimulates production of metalloprotease (MMP) and tissue inhibitor of MMP [121]
IFN type I/IL-10 IL-19 X - X Involved in both Th1 and Th2 inflammatory disorders [122,123]
      Possesses autocrine features [124,125]
  IL-20 X - X Overexpressed in psoriasis
      Possesses autocrine features [122]
  IL-22 X - - Relevant to innate immunity and acute-phase response [126]
  IL-24 X - - Possible antagonism with regulatory IL-10 [127]
  IL-26 X - - Polymorphism possibly contributes to RA sex-bias susceptibility [128]
  IL-28, IL-29 X - X Involved in microbial recognition by upregulation of Toll-like receptors
      Possesses autocrine features [30,129,130]
IL-12 IL-12 X - - Predominantly produced by synovial Mφ and dendritic cells
      Promotes Th1 responses (reviewed in [62])
  IL-23 X - - Predominantly produced by synovial Mφ and dendritic cells
      Shares p40 subunit with IL-12 and possibly antagonizes IL-12 [63] (reviewed in [62])
  IL-27 X X X Produced by Mφ and its neutralization has anti-arthritic effects
      Possesses autocrine features [66]
      Pro-inflammatory role [67]
IL-17 IL-17 X - - Th0-Th1 lymphokine with pleiotropic, amplifying effects on Mφ arthritis (reviewed in [24,25])
  1. IFN, interferon; LIF, leukemia inhibitory factor; Mφ, macrophages; RA, rheumatoid arthritis. Reproduced with permission from Kinne RW, Stuhlmuller B, Palombo-Kinne E, Burmester GR: The role of macrophages in rheumatoid arthritis. In Rheumatoid Arthritis. Edited by Firestein GS, Panayi GS, Wollheim FA. New York: Oxford University Press; 2006:55–75 [2].