Heme oxygenase-1 is dispensable for the anti-inflammatory activity of intravenous immunoglobulin

• Published in: Scientific reports Vol. 6; no. 1; p. 19592
• Main Authors: Galeotti, Caroline, Hegde, Pushpa, Das, Mrinmoy, Stephen-Victor, Emmanuel, Canale, Fernando, Muñoz, Marcos, Sharma, Varun K., Dimitrov, Jordan D., Kaveri, Srini V., Bayry, Jagadeesh
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.01.2016; Nature Publishing Group
• Subjects: 13/1; 13/21; 631/250/2504/342; 631/250/251; 631/250/256; 64/60; 82/29; 82/80; 96/106; Allergology; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Cytoprotection - drug effects; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Enzyme Induction - drug effects; Experimental allergic encephalomyelitis; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - metabolism; Humanities and Social Sciences; Humans; Immune system; Immunoglobulin G; Immunoglobulins; Immunoglobulins, Intravenous - pharmacology; Immunoglobulins, Intravenous - therapeutic use; Immunology; Inflammation; Innate immunity; Interleukin 6; Intravenous administration; Life Sciences; Liver; Lymphocytes B; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Monocytes; Monocytes - drug effects; Monocytes - metabolism; multidisciplinary; Nitric oxide; Oxygenase; Protective Agents - pharmacology; RAW 264.7 Cells; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep19592

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.