title: Inhibitory effect of IVIG on IL-17 production by Th17 cells is independent of anti-IL-17 antibodies in the immunoglobulin preparations.
abstract: OBJECTIVE
  Th17 cells and their cytokines play a critical role in the pathogenesis of various autoimmune and inflammatory diseases. Recently, we have demonstrated that intravenous immunoglobulin (IVIG) suppresses differentiation, amplification, and functions of human Th17 cells. In this report we investigated whether IVIG inhibits IL-17 production by Th17 cells cultured in the presence of IL-23 and whether the inhibitory effect of IVIG on IL-17 production implicates anti-IL-17 antibodies.
  
  
  METHODS
  Naive CD4(+) T cells were stimulated in the presence of TGF-β, IL-21, and IL-23 for the differentiation of Th17 cells. Memory CD4(+) T cells were stimulated with IL-1β, IL-6, and IL-23 for the amplification of Th17 cells. IVIG (0.15 mM) was added to the cells 12 h after initiation of cultures. IL-17A cytokine and anti-IL-17 antibodies were measured by ELISA.
  
  
  RESULTS
  IL-23 did not deter the inhibitory effect of IVIG on IL-17 production from the differentiating and expanding Th17 cells. Further, suppression of IL-17 by IVIG did not implicate anti-IL-17 antibodies in the immunoglobulin preparations.
  
  
  CONCLUSIONS
  The effect of IVIG on the inhibition of IL-17 production by Th17 cells is a consequence of modulation of Th17 cells and their intracellular signaling pathways and not due to passive neutralization of IL-17 by anti-IL-17 antibodies in the immunoglobulin preparations.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 872, 15 rue de l'Ecole de Médicine, Paris 75006, France.
authors.forename: Mohan S
authors.initials: MS
authors.lastname: Maddur
authors.forename: Meenu
authors.initials: M
authors.lastname: Sharma
authors.forename: Pushpa
authors.initials: P
authors.lastname: Hegde
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
mesh_terms: D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000302:isolation & purification / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology*; D053759:Interleukin-23 / Q000494:pharmacology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000906:Antibodies; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D020381:Interleukin-17; D053759:Interleukin-23