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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.

Original publication

DOI

10.1016/j.ajpath.2013.02.029

Type

Journal article

Journal

Am J Pathol

Publication Date

06/2013

Volume

182

Pages

2071 - 2081

Keywords

Acute Disease, Animals, Antibodies, Monoclonal, Brain, Contrast Media, Drug Evaluation, Preclinical, Encephalomyelitis, Autoimmune, Experimental, Female, Gadolinium DTPA, Gene Expression Regulation, Interleukin-17, Magnetic Resonance Imaging, Mice, Mice, Biozzi, Motor Activity, RNA, Messenger, Remission Induction, Secondary Prevention, Severity of Illness Index, Treatment Outcome, Vascular Cell Adhesion Molecule-1