Co-delivery of autoantigen and dexamethasone in incomplete Freund's adjuvant ameliorates experimental autoimmune encephalomyelitis

J Control Release. 2017 Nov 28:266:156-165. doi: 10.1016/j.jconrel.2017.09.034. Epub 2017 Sep 28.

Abstract

Current therapies for autoimmune diseases focus on treating the symptoms rather than the underlying disease cause. A major setback in improving current therapeutics for autoimmunity is the lack of antigen specificity. Successful antigen-specific immunotherapy (ASIT) would allow for improved treatment of autoimmune diseases. In this work, dexamethasone was co-delivered with autoantigen (PLP) in vivo to create effective ASIT for the treatment of experimental autoimmune encephalomyelitis (EAE). Using an emulsion of incomplete Freund's adjuvant (IFA) as a co-delivery vehicle, it was discovered that the controlled release of autoantigen was important for the suppression of clinical disease symptoms. Analysis of the immune response via cytokines revealed that dexamethasone was important for shifting the immune response away from inflammation. Co-delivery of both autoantigen and dexamethasone increased B-cell populations and antibody production, signifying an increased humoral immune response. Overall, this data indicated that the co-delivery of PLP and dexamethasone with a water-in-oil emulsion is effective in treating a murine autoimmune model.

Keywords: Antigen-specific immunotherapy; Co-delivery; Dexamethasone; Experimental autoimmune encephalomyelitis (EAE); Incomplete Freund's adjuvant (IFA); Proteolipid protein (PLP).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antibody Formation
  • Autoantigens / administration & dosage*
  • B-Lymphocytes / immunology
  • Cytokines / immunology
  • Dexamethasone / administration & dosage*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Freund's Adjuvant / administration & dosage*
  • Immunologic Factors / administration & dosage*
  • Lipids / administration & dosage*
  • Mice
  • Myelin Proteolipid Protein / administration & dosage*
  • Peptide Fragments / administration & dosage*
  • Spleen / cytology

Substances

  • Anti-Inflammatory Agents
  • Autoantigens
  • Cytokines
  • Immunologic Factors
  • Lipids
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • incomplete Freund's adjuvant
  • myelin proteolipid protein (139-151)
  • Dexamethasone
  • Freund's Adjuvant