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

Journal article

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.

Authors: Mardiguian, S; Serres, S; Ladds, E; Campbell, S; Wilainam, P

• Publication status: Published
• Journal: American journal of pathology
• Volume: 182
• Issue: 6
• Pages: 2071-2081
• Publication date: 2013-06-01
• DOI: 10.1016/j.ajpath.2013.02.029
• EISSN: 1525-2191
• ISSN: 0002-9440
• Language: English
• Keywords: Treatment Outcome; Drug Evaluation, Preclinical; Encephalomyelitis, Autoimmune, Experimental; Interleukin-17; Recurrence; Motor Activity; Acute Disease; Gadolinium DTPA; Female; Animals; Remission Induction; Mice; RNA, Messenger; Contrast Media; Mice, Biozzi; Severity of Illness Index; Vascular Cell Adhesion Molecule-1; Antibodies, Monoclonal; Gene Expression Regulation; Magnetic Resonance Imaging; Brain