title: Interleukin 10 hampers endothelial cell differentiation and enhances the effects of interferon α on lupus endothelial cell progenitors.
abstract: OBJECTIVE
  SLE is an autoimmune disease characterized by autoantibody generation, organ damage and an increased risk of cardiovascular disease. Generally considered an anti-inflammatory cytokine, IL-10 is increased in SLE and correlates with poor cardiovascular outcomes in the general population. The aim of this study was to explore the putative role of IL-10 in modulating endothelial function in SLE by examining the effects of this cytokine on endothelial progenitor cell/circulating angiogenic cell (EPC/CAC) differentiation.
  
  
  METHODS
  Human and murine control and lupus EPCs/CACs were differentiated into mature endothelial cells (ECs) in the presence or absence of graded concentrations of recombinant IL-10 with or without recombinant IFN-α or a neutralizing antibody to IL-10. IL-10-deficient mice were examined to assess the role of this cytokine in type I IFN-mediated inhibition of EC differentiation and neo-angiogenesis using an in vivo Matrigel plug assay. Serum IL-10 concentrations were measured via ELISA.
  
  
  RESULTS
  IL-10 hampers EC differentiation in a dose-dependent manner. In murine EPC cultures, IL-10 is required to observe the inhibitory effects of type I IFNs on EPC function and neo-angiogenesis. In human SLE EPC/CAC cultures, neutralization of IL-10 significantly improved the differentiation of EPCs, and IL-10 enhanced type I IFN-mediated EPC/CAC dysfunction. The presence of IL-10 in serum inversely correlated with EPC/CAC function in SLE but not in control cells.
  
  
  CONCLUSIONS
  IL-10 interferes with endothelial differentiation and may enhance the effects of type I IFN on vascular repair in SLE. IL-10 may be a relevant target for improving cardiovascular risk in SLE.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Cates
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Victoria I
authors.initials: VI
authors.lastname: Holden
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Myers
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carolyne K
authors.initials: CK
authors.lastname: Smith
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI and Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Disorders, National Institutes of Health, Bethesda, MD, USA mkahlenb@med.umich.edu.
authors.forename: J Michelle
authors.initials: JM
authors.lastname: Kahlenberg
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged
chemical_list: D016898:Interferon-alpha; D016753:Interleukin-10
keywords: IL-10; cardiovascular; endothelial progenitor; interferon α; lupus