title: Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE.
abstract: BACKGROUND
  Ingested immunoactive proteins type I IFN, SIRS peptide 1-21, α-MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T(reg) cell frequencies.
  
  
  OBJECTIVE
  We examined whether another protein, thyrotropin releasing factor (TRH), would have similar anti-inflammatory effects in EAE after oral administration.
  
  
  METHODS
  B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TRH during ongoing disease. Splenocytes from mock fed or TRH fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease.
  
  
  RESULTS
  Ingested (oral) TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TRH fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF-α cytokines in both the spleen and the CNS. In recipients of donor cells from TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in T(reg) cell frequencies in actively fed or recipients of TRH fed donor cells.
  
  
  CONCLUSIONS
  Ingested (orally administered) TRH can inhibit clinical disease, inhibit CNS inflammation by decreasing Th1-like, Th17 and TNF-α cytokines and increasing Th2-like cytokines (IL-13) in the CNS.
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: Victoria
authors.initials: V
authors.lastname: Bauer
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000134:cerebrospinal fluid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018793:Interleukin-13; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D013973:Thyrotropin-Releasing Hormone