title: Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis.
abstract: OBJECTIVE
  To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU).
  
  
  METHODS
  C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured.
  
  
  RESULTS
  AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression.
  
  
  CONCLUSIONS
  AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.
authors.affiliation: Retina Service, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.forename: Takeru
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Marina
authors.initials: M
authors.lastname: Simeonova
authors.forename: Kimio
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morizane
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Lucia
authors.initials: L
authors.lastname: Sobrin
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007111:Immunity, Cellular; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D012265:Ribonucleotides / Q000008:administration & dosage* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014602:Uvea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide