title: 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.
authors.affiliation: CR-UK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom.
authors.forename: Silvy
authors.initials: S
authors.lastname: Mardiguian
authors.forename: Sébastien
authors.initials: S
authors.lastname: Serres
authors.forename: Emma
authors.initials: E
authors.lastname: Ladds
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Campbell
authors.forename: Panop
authors.initials: P
authors.lastname: Wilainam
authors.forename: Charles
authors.initials: C
authors.lastname: McFadyen
authors.forename: Martina
authors.initials: M
authors.lastname: McAteer
authors.forename: Robin P
authors.initials: RP
authors.lastname: Choudhury
authors.forename: Paul
authors.initials: P
authors.lastname: Smith
authors.forename: Fay
authors.initials: F
authors.lastname: Saunders
authors.forename: Gillian
authors.initials: G
authors.lastname: Watt
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D003287:Contrast Media; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D019786:Gadolinium DTPA; D005786:Gene Expression Regulation; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D038602:Mice, Biozzi; D009043:Motor Activity; D012333:RNA, Messenger / Q000235:genetics; D012074:Remission Induction; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; C098680:Il17a protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D019786:Gadolinium DTPA