title: Recombinant soluble IFN receptor (sIFNAR2) exhibits intrinsic therapeutic efficacy in a murine model of Multiple Sclerosis.
abstract: Endogenous interferon beta (IFNβ) is an important cytokine involved in several chronic inflammatory diseases, such as Multiple Sclerosis (MS). In spite of the numerous therapeutic approaches available for MS patients, the administration of recombinant IFNβ continues being one of the first line treatment to these patients. The soluble form of IFNβ receptor (sIFNAR2) could act as critical regulator of the endogenous and the systemically administered IFNβ, but whether it functions as an agonist or antagonist of its ligand is not completely elucidated. Morover, the possible role of sIFNAR2 in autoimmune diseases like MS is still unknown and so far overlooked. Here we evaluated the efficacy of the combined therapy of IFNβ and our recombinant protein analogous to human sIFNAR2 as a treatment in a chronic mice model of MS (CP-EAE). We also tested the effect of the sIFNAR2 administered as a monotherapy over these EAE-animals. The results showed that our recombinant sIFNAR2 protein potentiates the immunomodulatory effects of exogenous IFNβ in CP-EAE by increasing the reduction of the induced inflammation and the tissue damage. Furthermore, we demonstrate for the first time that sIFNAR2 shows intrinsic properties by modulating the CP-EAE progression and the neuroinflammation processes related to this disease. Another intrinsic activity showed by sIFNAR2 is the inhibition of the T cells proliferation, which increase its potential as therapeutic molecule.
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: marga.suardiaz@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Suardíaz
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, 45071, Toledo, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: D
authors.initials: D
authors.lastname: Clemente
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Marin-Bañasco
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Orpez
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Hurtado-Guerrero
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, Instituto de Biomedicina de Málaga (IBIMA), 29009, Málaga, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pavía
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pinto-Medel
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, 45071, Toledo, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: F
authors.initials: F
authors.lastname: De Castro
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: L
authors.initials: L
authors.lastname: Leyva
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: O
authors.initials: O
authors.lastname: Fernández
authors.affiliation: Unidad de Gestión Clínica Inter-centros de Neurociencias, Laboratorio de Investigación y Servicio de Neurología, Instituto de Biomedicina de Málaga (IBIMA), Hospitales Universitarios Regional de Málaga y Virgen de la Victoria, 29009, Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.
authors.forename: B
authors.initials: B
authors.lastname: Oliver
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016899:Interferon-beta / Q000008:administration & dosage / Q000378:metabolism; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D053633:Receptor, Interferon alpha-beta / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013154:Spleen / Q000187:drug effects / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
chemical_list: C508033:IFNAR2 protein, human; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta
keywords: EAE; IFNAR; Interferon beta; Multiple Sclerosis; Soluble receptor