Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis

Arthritis Rheum. 2009 Apr;60(4):966-75. doi: 10.1002/art.24406.


Objective: Peripheral spondylarthritis (SpA) is characterized by macrophages that express CD163, a marker of alternative activation (M2). The purpose of this study was to assess whether this differential infiltration with macrophage subsets was associated with a different local inflammatory milieu in SpA as compared with rheumatoid arthritis (RA).

Methods: The effect of SpA and RA synovial fluid (SF) on macrophage polarization was tested in vitro on normal peripheral blood monocytes. SF levels of classically activated macrophage (M1)-derived and alternatively activated macrophage (M2)-derived mediators were analyzed by enzyme-linked immunosorbent assay and multiparameter Luminex bead assay in 47 patients with non-psoriatic SpA, 55 with RA, and 15 with psoriatic arthritis (PsA). Paired synovial biopsy samples were analyzed histologically.

Results: SF from SpA patients promoted preferential expression of the M2 markers CD163 and CD200R in vitro, even if SF levels of the prototypical M2-polarizing factors (interleukin-4 [IL-4], IL-13, and IL-10) were not increased as compared with those in RA SF. Despite a similar degree of overall joint inflammation in SpA and RA, SpA synovitis displayed strongly reduced SF levels of M1-derived, but not M2-derived, mediators, such as tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-12p70, and interferon-gamma-inducible protein 10. SF levels of M1-derived mediators correlated well with peripheral joint inflammation in RA, but neither these mediators nor IL-1alpha and IL-17 did so in SpA. Of interest, the SF cytokine profile in PsA, a more destructive subtype of SpA, was similar to that in non-psoriatic SpA.

Conclusion: The local inflammatory milieu is clearly different in SpA as compared with RA peripheral arthritis. Synovitis in SpA, including that in PsA, is characterized by a selective decrease in M1-derived proinflammatory mediators, such as TNFalpha and IL-1beta.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Psoriatic / immunology*
  • Arthritis, Psoriatic / pathology
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / metabolism
  • Biopsy
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Female
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Spondylarthritis / immunology*
  • Spondylarthritis / pathology
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology


  • Biomarkers
  • Cytokines