title: Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Vandooren
authors.forename: Troy
authors.initials: T
authors.lastname: Noordenbos
authors.forename: Carmen
authors.initials: C
authors.lastname: Ambarus
authors.forename: Sarah
authors.initials: S
authors.lastname: Krausz
authors.forename: Tineke
authors.initials: T
authors.lastname: Cantaert
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yeremenko
authors.forename: Maartje
authors.initials: M
authors.lastname: Boumans
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten