title: In vivo pre-activation of monocytes in patients with axial spondyloarthritis.
abstract: BACKGROUND
  Innate immune responses, including monocyte functions, seem to play an important role in the pathogenesis of axial spondyloarthritis (axSpA). Therefore, we characterized the phenotype and functional state of monocytes of patients with axSpA.
  
  
  METHODS
  Fifty-seven patients with axSpA, 11 patients with rheumatoid arthritis (RA), and 29 healthy controls were included in the study. We determined the percentage of classic, intermediate, and non-classic monocytes according to CD14 and CD16 expression and the expression of Toll-like receptor (TLR) 1, 2, and 4 in whole blood by flow cytometry. The percentage of monocytes producing interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNFα), IL-12/23p40, and IL-1 receptor antagonist (IL-1ra) was detected by flow cytometry after stimulation of whole blood without and with different TLR and nucleotide-binding oligomerization domain ligands-i.e., lipopolysaccharide (LPS), fibroblast-stimulating lipopeptid-1, PAM3CSK4, and muramyl dipeptide (MDP)-for 5 h. IL-10 production was measured after 18 h of stimulation in supernatants by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In patients with axSpA but not patients with RA, we found higher frequencies of classic monocytes than in controls (median of 90.4% versus 80.4%, P < 0.05), higher frequencies of monocytes spontaneously producing IL-1beta and IL-1ra (P < 0.05), and a higher percentage of monocytes producing IL-1beta after MDP stimulation (P < 0.05). Elevated cytokine production was confined to axSpA patients under conventional therapy (non-steroidal anti-inflammatory drugs) and not found in patients under TNFα inhibitor treatment. The LPS-induced production of IL-6 and IL-10 was lower in axSpA patients compared with controls (P < 0.05). Monocytic TLR expression was unaffected in patients with axSpA.
  
  
  CONCLUSIONS
  Enhanced spontaneous and MDP-induced cytokine secretion by monocytes suggests in vivo pre-activation of monocytes in axSpA patients under conventional therapy which is reverted under TNF inhibitor treatment.
authors.affiliation: Charité-Universitätsmedizin Berlin, CBF, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, Berlin, 12203, Germany. kristin.conrad@web.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Conrad
authors.affiliation: Deutsches Rheumaforschungszentrum, Charitéplatz 1, Berlin, 10117, Germany. peihua.wu@charite.de.
authors.forename: Peihua
authors.initials: P
authors.lastname: Wu
authors.affiliation: Charité-Universitätsmedizin Berlin, CBF, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, Berlin, 12203, Germany. joachim.sieper@charite.de.|Deutsches Rheumaforschungszentrum, Charitéplatz 1, Berlin, 10117, Germany. joachim.sieper@charite.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.affiliation: Charité-Universitätsmedizin Berlin, CBF, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, Berlin, 12203, Germany. uta.syrbe@charite.de.|Deutsches Rheumaforschungszentrum, Charitéplatz 1, Berlin, 10117, Germany. uta.syrbe@charite.de.
authors.forename: Uta
authors.initials: U
authors.lastname: Syrbe
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000378:metabolism*; D001368:Axis, Cervical Vertebra / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D025241:Spondylarthritis / Q000175:diagnosis* / Q000378:metabolism*
chemical_list: D016207:Cytokines