title: Heme oxygenase-1 is dispensable for the anti-inflammatory activity of intravenous immunoglobulin.
abstract: Intravenous immunoglobulin G (IVIG) is used in the therapy of various autoimmune and inflammatory conditions. The mechanisms by which IVIG exerts anti-inflammatory effects are not completely understood. IVIG interacts with numerous components of the immune system including dendritic cells, macrophages, T and B cells and modulate their functions. Recent studies have reported that heme oxygenase-1 (HO-1) pathway plays an important role in the regulation of inflammatory response in several pathologies. Several therapeutic agents exert anti-inflammatory effects via induction of HO-1. Therefore, we aimed at exploring if anti-inflammatory effects of IVIG are mediated via HO-1 pathway. Confirming the previous reports, we report that IVIG exerts anti-inflammatory effects on innate cells as shown by the inhibitory effects on IL-6 and nitric oxide production and confers protection in experimental autoimmune encephalomyelitis (EAE) model. However, these effects were not associated with an induction of HO-1 either in innate cells such as monocytes, dendritic cells and macrophages or in the kidneys and liver of IVIG-treated EAE mice. Also, inhibition of endogenous HO-1 did not modify anti-inflammatory effects of IVIG. These results thus indicate that IVIG exerts anti-inflammatory effects independent of HO-1 pathway.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.|Department of Pediatric Rheumatology, National Referral Centre of Auto-inflammatory Diseases, CHU de Bicêtre, le Kremlin Bicêtre, F-94270, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Galeotti
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Hegde
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Mrinmoy
authors.initials: M
authors.lastname: Das
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stephen-Victor
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Canale
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Marcos
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.
authors.forename: Varun K
authors.initials: VK
authors.lastname: Sharma
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.|Université Paris Descartes, Sorbonne Paris Cité, UMR S 1138, Paris, F-75006, France.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.|Université Paris Descartes, Sorbonne Paris Cité, UMR S 1138, Paris, F-75006, France.|International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian council of Medical Research, India), National Institute of Immunohaematology, Mumbai, 400012, India.
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 1138, Paris, F-75006, France.|Sorbonne Universités, UPMC Univ Paris 06, UMR S 1138, Paris, F-75006, France.|Centre de Recherche des Cordeliers, Equipe - Immunopathology and therapeutic immunointervention, Paris, F-75006, France.|Université Paris Descartes, Sorbonne Paris Cité, UMR S 1138, Paris, F-75006, France.|International Associated Laboratory IMPACT (Institut National de la Santé et de la Recherche Médicale, France - Indian council of Medical Research, India), National Institute of Immunohaematology, Mumbai, 400012, India.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D016756:Immunoglobulins, Intravenous; D020011:Protective Agents; D051547:Heme Oxygenase-1