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Brain Advance Access originally published online on September 8, 2004
Brain 2004 127(12):2649-2656; doi:10.1093/brain/awh297
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Brain Vol. 127 No. 12 © Guarantors of Brain 2004; all rights reserved

IVIg therapy in brain inflammation: etiology-dependent differential effects on leucocyte recruitment

Benoît M. Lapointe1, Leonie M. Herx1, Varinder Gill1, Luanne M. Metz2 and Paul Kubes1

1 Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary and 2 Department of Clinical Neurosciences, Foothills Hospital, Calgary, Alberta, Canada

Correspondence to: Dr Paul Kubes, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1 E-mail: pkubes{at}ucalgary.ca

Several studies have reported beneficial effects of intravenous immunoglobulin (IVIg) in diseases of the neuroaxis. However, IVIg effects on leucocyte recruitment, a hallmark feature of autoimmunity and acute inflammation, remain largely unexplored. Using intravital microscopy, we studied the effects of IVIg on leucocyte recruitment in experimental autoimmune encephalomyelitis, a model of multiple sclerosis. In IVIg-treated mice, a significant decrease in recruitment (rolling and adhesion) was observed prior to and following disease onset, and this was concomitant with improved clinical score. Since much of the recruitment is dependent upon {alpha}4-integrin (ligand for VCAM-1) we used an in vitro flow chamber system and demonstrated a 60% decrease in {alpha}4-integrin-dependent leucocyte adhesion to immobilized VCAM-1. Finally, we used leucocytes from multiple sclerosis patients and demonstrated that IVIg treatment decreased recruitment by 60% on human endothelium. However, when we visualized the role of IVIg in a second model of brain inflammation, cerebral ischaemia–reperfusion, IVIg actually promoted the formation of platelet–leucocyte aggregates in post-ischaemic cerebral vessels. In conclusion, we report a new mechanism of action of IVIg through interference of {alpha}4-integrin-dependent leucocyte recruitment in both an animal model and human multiple sclerosis. We also report that IVIg will not be beneficial in all types of pro-adhesive states and may in fact be detrimental in a situation such as stroke.


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