Skip Navigation



Brain Advance Access published online on September 8, 2004
Brain, doi:10.1093/brain/awh297
© 2004 by Guarantors of Brain
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
127/12/2649    most recent
awh297v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lapointe, B. M.
Right arrow Articles by Kubes, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lapointe, B. M.
Right arrow Articles by Kubes, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received May 6, 2004
Revised July 25, 2004
Accepted July 28, 2004

Article

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

Benoît M. Lapointe 1, Leonie M. Herx 1, Varinder Gill 1, Luanne M. Metz 2, and Paul Kubes 1*

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

* To whom correspondence should be addressed. E-mail: pkubes{at}ucalgary.ca.


  Abstract

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.

Keywords: multiple sclerosis; stroke; intravital; rolling; adhesion.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
H. Zhou, B. M. Lapointe, S. R. Clark, L. Zbytnuik, and P. Kubes
A Requirement for Microglial TLR4 in Leukocyte Recruitment into Brain in Response to Lipopolysaccharide
J. Immunol., December 1, 2006; 177(11): 8103 - 8110.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
H F Petereit, D Reske, R Pukrop, M Maas-Enriquez, G Japp, P J. Jongen, H W Kolmel, S Merkelbach, H P Hartung, W D Heiss, et al.
No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis
Multiple Sclerosis, February 1, 2006; 12(1): 66 - 71.
[Abstract] [PDF]

Home page
 CirculationHome page
K. Y. Stokes and D. N. Granger
Gaining More From Gamma Globulins
Circulation, September 27, 2005; 112(13): 1918 - 1920.
[Full Text] [PDF]

Home page
 LupusHome page
D J. McCabe, S Sumaria, and L A Wilson
Letter to the Editor
Lupus, May 1, 2005; 14(5): 409 - 410.
[PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.