title: Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFalpha.
abstract: OBJECTIVE
  To evaluate the effect of anti-TNFalpha on the Th1 and Th2 cytokines in patients with spondyloarthropathy (SpA).
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with active SpA treated with infliximab (5 mg/kg). For comparison, PBMC were also obtained from 15 healthy controls and 19 patients with active rheumatoid arthritis (RA). After stimulation with PMA/ionomycin, the intracellular cytokines interleukin (IL)2, IL4, IL10, and interferon (IFN)gamma were determined in CD3+ T cells and in CD3+/CD56+ natural killer (NK) T cells by flow cytometry.
  
  
  RESULTS
  At baseline the percentage of T cells positive for IFNgamma (p=0.020) and IL2 (p=0.046) was decreased in patients with SpA compared with healthy controls, while IL10 (p=0.001) was increased. This cytokine profile, confirmed by the mean fluorescence intensities (MFI), was more pronounced in CD3+/CD8- cells and contrasted with higher IL2 production in RA. NK T cells, characterised by high IL4 and IL10 numbers, were also increased in patients with SpA (p=0.017). Treatment with infliximab induced a significant and persistent increase in IFNgamma and IL2 in patients with SpA. Moreover, there was a transient decrease in IL10 and NK T cells in patients with high baseline values, resulting in values comparable with those of healthy controls. This switch in cytokine profile was seen in both the CD3+/CD8- and CD3+/CD8+ subsets.
  
  
  CONCLUSIONS
  Before treatment patients with SpA had an impaired Th1 cytokine profile compared with healthy controls and patients with RA. TNFalpha blockade induced restoration of the Th1 cytokines, resulting in a normal cytokine balance. These data confirm the effect of anti-TNFalpha on the immune changes in SpA, and provide insights into the mechanisms involved in TNFalpha blockade.
authors.affiliation: Department of Rheumatology, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium. dominique.baeten@rug.ac.be
authors.forename: D
authors.initials: D
authors.lastname: Baeten
authors.forename: N
authors.initials: N
authors.lastname: Van Damme
authors.forename: F
authors.initials: F
authors.lastname: Van den Bosch
authors.forename: E
authors.initials: E
authors.lastname: Kruithof
authors.forename: M
authors.initials: M
authors.lastname: De Vos
authors.forename: H
authors.initials: H
authors.lastname: Mielants
authors.forename: E M
authors.initials: EM
authors.lastname: Veys
authors.forename: F
authors.initials: F
authors.lastname: De Keyser
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013122:Spinal Diseases / Q000188:drug therapy* / Q000378:metabolism; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D000069285:Infliximab