| Autor: |
Mardiguian, Silvy, Serres, Sébastien, Ladds, Emma, Campbell, Sandra J., Wilainam, Panop, McFadyen, Charles, McAteer, Martina, Choudhury, Robin P., Smith, Paul, Saunders, Fay, Watt, Gillian, Sibson, Nicola R., Anthony, Daniel C. |
| Zdroj: |
American Journal of Pathology; June 2013, Vol. 182 Issue: 6 p2071-2081, 11p |
| Abstrakt: |
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. |
| Databáze: |
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