Recombinant soluble IFN receptor (sIFNAR2) exhibits intrinsic therapeutic efficacy in a murine model of Multiple Sclerosis

Endogenous interferon beta (IFN beta) 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 IFN beta continues being one of the first line treatment to these patients. The soluble form of IFN beta receptor (sIFNAR2) could act as critical regulator of the endogenous and the systemically administered IFN beta, 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 IFN beta 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 IFN beta 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. (C) 2016 Elsevier Ltd. All rights reserved.