title: Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation.
abstract: OBJECTIVE
  Several clinical studies performed with human recombinant interleukin 10 (IL-10) in patients with rheumatoid arthritis (RA) have shown little efficacy. We investigated potentially proinflammatory in vivo effects of IL-10 in humans. We evaluated the upregulation of Fc gamma receptor (Fc gamma R) expression on monocytes/macrophages (and granulocytes) in patients with RA receiving different dosages of IL-10.
  
  
  METHODS
  Together with changes in disease activity and several cell markers, the expression of Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII was determined on granulocytes and monocytes/macrophages from the peripheral blood of 6 patients with active RA before and after treatment with recombinant human IL-10. In addition, the in vitro effect of IL-10 on Fc gamma R expression on monocytes/macrophages in combination with their susceptibility to immune complex induced production of tumor necrosis factor-alpha(TNF-alpha) was assessed.
  
  
  RESULTS
  Clinical improvement was not observed in the IL-10 treated patients (based on ACR20 criteria). Significant decreases in thrombocyte numbers were observed in patients receiving IL-10. No changes in cell markers such as CD14 were found. On the other hand, expression of Fc gamma RI and Fc gamma RIIa on monocytes/macrophages was increased upon high dose IL-10 treatment. Interestingly, increases in expression of Fc gamma RI and Fc gamma RIIa correlated with a decrease in thrombocyte numbers. In vitro, IL-10 similarly upregulated Fc gamma RI and Fc gamma RIIa expression on monocytes/macrophages from RA patients. This was accompanied by increased TNF-a production after immune complex stimulation.
  
  
  CONCLUSIONS
  These findings indicate that upregulation of Fc gamma R expression in RA with IL-10 treatment may counteract the otherwise antiinflammatory effects of IL-10 by potentiating immune complex mediated proinflammatory responses.
authors.affiliation: Department of Reumatology and Clinical Immunology, University Medical Centre Utrecht, The Netherlands. J.vanRoon@azu.nl
authors.forename: Joel
authors.initials: J
authors.lastname: van Roon
authors.forename: Siska
authors.initials: S
authors.lastname: Wijngaarden
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.forename: Cora
authors.initials: C
authors.lastname: Damen
authors.forename: Jan
authors.initials: J
authors.lastname: van de Winkel
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D002097:C-Reactive Protein / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000008:administration & dosage / Q000009:adverse effects*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D017452:Receptors, IgG; D016753:Interleukin-10; D002097:C-Reactive Protein