title: In situ analysis of interleukin-23- and interleukin-12-positive cells in the spine of patients with ankylosing spondylitis.
abstract: OBJECTIVE
  The interleukin-12 (IL-12) family of cytokines has been suggested to play a critical role in inflammatory autoimmune diseases, and recent studies analyzing peripheral blood and synovial fluid from patients with spondyloarthritides suggest that IL-23 might be a proinflammatory factor in these disorders. This study was undertaken to investigate the presence and source of IL-23 in the spines of patients with ankylosing spondylitis (AS).
  
  
  METHODS
  The frequency of IL-23-positive and IL-12-positive cells within the subchondral bone marrow and within fibrous tissue replacing normal bone marrow in facet joints of patients with AS was analyzed by immunohistochemistry. The origin of IL-23-positive cells was determined by double staining of CD163+ macrophages, CD68+ macrophages, CD1a+ dendritic cells, tryptase-positive mast cells, myeloperoxidase-positive cells, CD20+ B cells, and CD3+ T cells. Findings in 28 facet joints from 22 AS patients were compared with those in 20 facet joints from 13 patients with osteoarthritis (OA) and 10 normal control specimens.
  
  
  RESULTS
  The frequency of IL-23-positive cells in subchondral bone marrow from the joints of AS patients (mean ± SD 42.50 ± 32.81/high-power field [hpf]) was significantly increased compared to that in subchondral bone marrow from OA patients (OA 15.63 ± 29.90/hpf) (P = 0.0017) or controls (19.36 ± 16.8/hpf) (P = 0.03). Myeloperoxidase-positive cells and, to a lesser extent, macrophages and dendritic cells were found to be the origin of IL-23 in the bone marrow. In AS and OA patients, the frequency of IL-23-positive cells was significantly higher than that of IL-12-positive cells (P < 0.001 in both patient groups). Within fibrous tissue from AS and OA facet joints, IL-23 was predominantly produced by CD163+ macrophages (mean ± SD 0.64 ± 0.59/hpf and 4.36 ± 3.4/hpf, respectively) and CD68+ macrophages (2.3 ± 0.65/hpf and 6.54 ± 4.1/hpf, respectively).
  
  
  CONCLUSIONS
  IL-23 is expressed in the subchondral bone marrow and in fibrous tissue replacing bone marrow in facet joints of patients with AS. It might have a role in inflammatory processes and in chronic changes in AS joints, which makes it an interesting potential therapeutic target in this disease.
authors.affiliation: Charité Berlin, Campus Benjamin Franklin, Berlin, Germany. heiner.appel@charite.de
authors.forename: Heiner
authors.initials: H
authors.lastname: Appel
authors.forename: Rene
authors.initials: R
authors.lastname: Maier
authors.forename: Janine
authors.initials: J
authors.lastname: Bleil
authors.forename: Axel
authors.initials: A
authors.lastname: Hempfing
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlichting
authors.forename: Uta
authors.initials: U
authors.lastname: Syrbe
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D007596:Joints / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013131:Spine / Q000276:immunology / Q000473:pathology*; D013167:Spondylitis, Ankylosing / Q000276:immunology*
chemical_list: D016207:Cytokines; D053759:Interleukin-23; D018664:Interleukin-12