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

Caroline Galeotti,Marcos Muñoz,Pushpa Hegde,Srini V Kaveri,Fernando Canale,Jordan D Dimitrov,Emmanuel Stephen-Victor,Jagadeesh Bayry,Varun K Sharma,Mrinmoy Das

doi:10.1038/srep19592

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.

Highlights

CO and biliverdin have potent anti-inflammatory, anti-proliferative, anti-apoptotic, and antioxidant activities and exert their effects on many cell types, including cells of the immune system[32]
Anti-inflammatory effects of IVIG on human monocytes are not associated with induction of HO-1
It is known that IVIG exerts anti-inflammatory effects on innate cells such as monocytes, dendritic cells (DCs) and macrophages leading to suppression of inflammatory cytokines[8,37,38,39]

Summary

Introduction

CO and biliverdin have potent anti-inflammatory, anti-proliferative, anti-apoptotic, and antioxidant activities and exert their effects on many cell types, including cells of the immune system[32]. CO suppresses the pro-inflammatory response and promotes the anti-inflammatory programs of macrophages, DCs and monocytes[33,34]. Either overexpression of HO-1 in innate cells or exposure to CO leads to inhibition of pro-inflammatory cytokines and enhancement of IL-10. CO inhibits the lipopolysaccharide (LPS)-mediated maturation of DCs35,36. In view of the common anti-inflammatory role exerted by both HO-1 and IVIG, we investigated if mechanisms of action of IVIG both in vitro and in vivo implicate HO-1 pathway

Methods

Results

Conclusion