title: Ingested (oral) ACTH inhibits EAE.
abstract: Ingested type I IFN and SIRS peptide inhibit EAE. We examined whether another immunoactive protein, ACTH, would have similar anti-inflammatory effects in EAE after oral administration. B6 mice were immunized and gavaged with control saline or ACTH starting on the onset of disease. ACTH decreased clinical score and decreased inflammatory foci. CNS lymphocytes showed decreases in IL-17 (T(eff)) and Th1-like encephalitogenic cytokines IL-2 and IFN-γ in the ACTH fed group compared to the mock fed group. Adoptive transfer of ACTH fed splenocytes into MOG immunized recipient mice with early clinical disease suppressed disease severity compared to splenocytes from mock fed donors. The protected recipients showed decreased splenic IL-17 (T(eff)) and Th1-like cytokine IFN-γ and increased CNS secretion of immunoregulatory IL-4 and chemokine M-CSF. Splenic CD4+CD25+ FoxP3+ frequency doubled in ACTH fed compared to control fed mice. Increased immuno-regulatory IL-4 and M-CSF secreting cell populations is the mechanism of protection in adoptively protected recipients and reflects the direct action of ACTH on the immune system.
authors.affiliation: Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States. staley.a.brod@uth.tmc.edu
authors.forename: Staley A
authors.initials: SA
authors.lastname: Brod
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Hood
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D006728:Hormones / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006728:Hormones; D000324:Adrenocorticotropic Hormone