Ingested (oral) anti-IL-12/23 inhibits EAE. J Neurol Sci 2016 Feb 15;361:19-25
Date
01/27/2016Pubmed ID
26810510DOI
10.1016/j.jns.2015.12.011Scopus ID
2-s2.0-84958957357 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
BACKGROUND: Blocking the activity of IL-12/23 can inhibit autoimmune diseases such as psoriasis.
OBJECTIVE: We examined whether an antibody against IL-12/23, ustekinumab (UTZ) (Stelera®), used clinically in psoriasis would have similar anti-inflammatory effects in EAE after oral administration.
DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with isotype IgG control or UTZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or UTZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses.
RESULTS: Ingested (oral) UTZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from UTZ fed donors protected against actively induced disease and decreased inflammation. Oral UTZ decreased pro-inflammatory cytokines Th1-like cytokines IL-2, IL-12, IFN-γ, IL-17 (Teff) and TNF-α in UTZ fed mice and increased counter-regulatory cytokines IL-4, IL-10 and IL-13 in recipients of donor cells from UTZ fed mice.
CONCLUSIONS: Ingested (orally administered) UTZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like and Th17 cytokines and increase Th2-like anti-inflammatory cytokines.
Author List
Brod SAMESH terms used to index this publication - Major topics in bold
Administration, OralAdoptive Transfer
Animals
Cytokines
Encephalomyelitis, Autoimmune, Experimental
Mice
Monocytes
Spinal Cord
Spleen
Th1 Cells
Th17 Cells
Ustekinumab
