title: Interleukin-10 inhibits the capacity of synovial macrophages to function as antigen-presenting cells.
abstract: OBJECTIVE
  We have investigated the effects of interleukin (IL)-10, IL-4 + granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha) on the phenotype and antigen-presenting capacity of synovial fluid (SF) macrophages from patients with rheumatoid arthritis.
  
  
  METHODS
  The effects of IL-4, IL-10, GM-CSF and TNF-alpha on the expression of surface antigens on SF macrophages were studied using flow cytometry. The effects of these cytokines on the capacity of SF macrophages to activate T cells was investigated using the allogeneic mixed lymphocyte reaction (MLR).
  
  
  RESULTS
  IL-10 reduced the expression of CD40, CD86 and HLA-DR, and increased the expression of CD14, on SF macrophages. IL-10 had no effect on the expression of CD80. Importantly, these effects of IL-10 on the phenotype of SF macrophages appear to have functional consequences, because cells incubated with IL-10 had a significantly reduced capacity to activate T cells in MLR. The effects of IL-4, GM-CSF and TNF-alpha were generally opposite to those observed in response to IL-10. IL-4 + GM-CSF, a combination of cytokines known to induce differentiation of dendritic cells, increased the expression of CD40, CD80 and CD86, and decreased the expression of CD14 on SF macrophages. Accordingly, IL-4 + GM-CSF increased the capacity of SF macrophages to activate T cells in MLR. IL-10 inhibited the effects of IL-4 + GM-CSF on SF macrophages.
  
  
  CONCLUSIONS
  IL-10 inhibits the antigen-presenting capacity of SF macrophages, which further emphasizes the anti-inflammatory potential of IL-10 in RA. Importantly, IL-10 is able to downregulate the APC function of SF macrophages even when they are efficiently activated.
authors.affiliation: Turku Immunology Centre, Department of Medical Microbiology, Turku University, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Möttönen
authors.forename: P
authors.initials: P
authors.lastname: Isomäki
authors.forename: R
authors.initials: R
authors.lastname: Saario
authors.forename: P
authors.initials: P
authors.lastname: Toivanen
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: O
authors.initials: O
authors.lastname: Lassila
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D018122:B7-1 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor