title: High levels of interleukin 13 in rheumatoid arthritis sera are modulated by tumor necrosis factor antagonist therapy: association with dendritic cell growth activity.
abstract: OBJECTIVE
  To investigate the physiology of interleukin 13 (IL-13) in rheumatoid arthritis (RA) and the effects of tumor necrosis factor (TNF) antagonists (etanercept) on the distribution of IL-13 in patients with RA.
  
  
  METHODS
  We measured cytokine levels in RA sera (pre/post etanercept), RA synovial fluid (SF), osteoarthritis (OA) SF, and normal human sera by ELISA. Detection of IL-13 was not influenced by rheumatoid factor, as revealed in spike recovery and isotype antibody control studies. Biologically active IL-13 in RA SF was studied using dendritic cell (DC) progenitors that develop into mature DC with IL-13 and with neutralizing antibodies to IL-13. The modulation of IL-13 by etanercept was compared to that of IL-6 and monocyte colony stimulating factor (M-CSF). The effect of etanercept on the ability of RA sera to promote DC growth was studied using DC progenitors.
  
  
  RESULTS
  IL-13 was increased in RA sera versus normal sera, OA SF, and RA SF. Relative to OA SF and normal sera, RA SF was enriched in IL-13. The IL-13 contained in RA samples was biologically active, prompting DC growth from progenitors. Circulating DC growth activity was strongly reduced by anti-TNF therapy. Whereas decreases in DC growth factors including IL-13 and IL-6 occurred with etanercept therapy and were associated with clinical improvement, concurrent increases in circulating M-CSF (a non-DC, monocyte-specific growth factor) were noted.
  
  
  CONCLUSIONS
  The increase of biologically active IL-13 in RA supports the concept that IL-13 regulates immune cell (including dendritic cell) activity and indicates how the varied anatomical distribution of cytokines may play a role in the RA disease process. The differential regulation of circulating IL-13 and M-CSF levels by TNF antagonists further implies discrete roles in the TNF-cytokine network in RA.
authors.affiliation: Winthrop University Hospital, Mineola, New York 11501, USA.
authors.forename: Amiel
authors.initials: A
authors.lastname: Tokayer
authors.forename: Steven E
authors.initials: SE
authors.lastname: Carsons
authors.forename: Binny
authors.initials: B
authors.lastname: Chokshi
authors.forename: Frances
authors.initials: F
authors.lastname: Santiago-Schwarz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000628:therapy*; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000032:analysis / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018793:Interleukin-13; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D000068800:Etanercept