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Anti-IL-17A treatment reduces clinical score and VCAM-1 expression detected by in vivo magnetic resonance imaging in chronic relapsing EAE ABH mice.

Abstract
IL-17 is argued to play an important role in the multiple sclerosis-like disease experimental autoimmune encephalitis (EAE). We investigated the therapeutic effects of anti-IL-17A in a chronic relapsing EAE ABH mouse model using conventional scoring, quantitative behavioral outcomes, and a novel vascular cell adhesion molecule 1 (VCAM-1)-targeted magnetic resonance imaging (MRI) contrast agent [anti-VCAM-microparticles of iron oxide (MPIO)] to identify conventionally undetectable neuropathology. Mice were administered prophylactic or treatment regimens of anti-IL-17A or IgG and two injections of anti-VCAM-MPIO before undergoing T2*-weighted three-dimensional and gadolinium-diethylenetriamine pentaacetic acid T1-weighted MRI. Rotarod, inverted screen, and open field motor function tests were performed, conventional clinical scores calculated, and central IL-17A mRNA expression quantified during acute disease, remission, and relapse. Prophylactic anti-IL-17A prevents acute disease and relapse and is associated with reduced clinical and functional severity. Treatment regimens delay relapse, improve functional scores, and are associated with reduced VCAM-MPIO lesions during remission. No significant alteration was detectable in levels of gadolinium-diethylenetriamine pentaacetic acid- or VCAM-MPIO-positive lesions during relapse. Prophylactic and treatment anti-IL-17A were therapeutically effective in chronic relapsing EAE, improving clinical and quantifiable functional outcomes. IL-17A expression seems significant during acute disease but less important chronically. Disease-related immunoneuropathology is more sensitively detected using VCAM-MPIO MRI, which may, therefore, be used to monitor therapy meaningfully.
AuthorsSilvy Mardiguian, Sébastien Serres, Emma Ladds, Sandra J Campbell, Panop Wilainam, Charles McFadyen, Martina McAteer, Robin P Choudhury, Paul Smith, Fay Saunders, Gillian Watt, Nicola R Sibson, Daniel C Anthony
JournalThe American journal of pathology (Am J Pathol) Vol. 182 Issue 6 Pg. 2071-81 (Jun 2013) ISSN: 1525-2191 [Electronic] United States
PMID23602647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antibodies, Monoclonal
  • Contrast Media
  • Il17a protein, mouse
  • Interleukin-17
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • Gadolinium DTPA
Topics
  • Acute Disease
  • Animals
  • Antibodies, Monoclonal (therapeutic use)
  • Brain (metabolism)
  • Contrast Media
  • Drug Evaluation, Preclinical (methods)
  • Encephalomyelitis, Autoimmune, Experimental (metabolism, pathology, therapy)
  • Female
  • Gadolinium DTPA
  • Gene Expression Regulation
  • Interleukin-17 (antagonists & inhibitors, biosynthesis, genetics)
  • Magnetic Resonance Imaging (methods)
  • Mice
  • Mice, Biozzi
  • Motor Activity
  • RNA, Messenger (genetics)
  • Remission Induction
  • Secondary Prevention
  • Severity of Illness Index
  • Treatment Outcome
  • Vascular Cell Adhesion Molecule-1 (metabolism)

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