title: Therapeutic gene silencing with siRNA for IL-23 but not for IL-17 suppresses the development of experimental autoimmune encephalomyelitis in rats.
abstract: Gene silencing with siRNAs is important as a therapeutic tool in autoimmune diseases. In this study, we administered siRNAs specific for cytokines that may be involved in pathogenesis of experimental autoimmune encephalomyelitis (EAE). siRNA specific for IL-23p19 (siRNA-IL-23) suppressed EAE almost completely, whereas siRNA-IL-17A did not modulate the clinical course. Flow cytometric analysis revealed that siRNA-IL-23 significantly reduced the proportion of both IFN-γ(+)IL-17(-) Th1 and IFN-γ(-)IL-17(+) Th17 cells in the spinal cord. Consistent with this finding, siRNA-IL-23 treatment downregulated IL-12, IL-17 and IL-23 mRNAs. These findings indicate that IL-23, but not IL-17, play an important role in the development of EAE.
authors.affiliation: Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Niimi
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kohyama
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000009:adverse effects; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018664:Interleukin-12; D005620:Freund's Adjuvant