title: sHLA-I Contamination, a novel mechanism to explain ex vivo/in vitro modulation of IL-10 synthesis and release in CD8(+) T lymphocytes and in neutrophils following intravenous immunoglobulin infusion.
abstract: BACKGROUND
  Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.
  
  
  METHODS
  Ex vivo analysis of cells from ten IVIG recipients showed significant increase of IL-10 mRNA and intra-cellular IL-10 molecules in both leukotypes.
  
  
  RESULTS
  In vitro comparable results were obtained incubating CD8(+) T lymphocytes and neutrophils from healthy donors with IVIG. sHLA-I and/or sFasL immunodepletion abolished IL-10 modulation. Co-culture with contaminant-free IgM or MabThera did not exert any mRNA modulation. Finally, IgM or MabThera plus purified sHLA-I molecules enhanced IL-10-mRNA in both leukotypes to levels comparable to those obtained with IVIG incubation.
  
  
  CONCLUSIONS
  As IVIG infusion involves administration of soluble contaminants, these data consent to speculate that IVIG might modulate IL-10 via the immunomodulatory activities of sHLA-I contaminant molecules inducing transcriptional and post-transcriptional modulation of IL-10 in CD8(+) T lymphocytes and neutrophils.
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, University of Genoa Medical School, 16132, Genoa, Italy. mghio@unige.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghio
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Setti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ubezio
authors.forename: Clemente
authors.initials: C
authors.lastname: Mazzei
authors.forename: Gino
authors.initials: G
authors.lastname: Tripodi
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D004340:Drug Contamination; D053222:Fas Ligand Protein / Q000378:metabolism / Q000494:pharmacology; D015673:Fatigue Syndrome, Chronic / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000378:metabolism; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D056647:Systemic Vasculitis / Q000276:immunology / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10