title: Suppression of experimental autoimmune uveitis by angiotensin II type 1 receptor blocker telmisartan.
abstract: OBJECTIVE
  Angiotensin II type 1 receptor (AT1-R) blockers are used widely for the treatment of patients with hypertension. Recent reports have suggested that AT1-R also plays a key role in various inflammatory conditions. The aim of this study was to examine whether blockade of AT1-R is effective in the suppression of murine experimental autoimmune uveoretinitis (EAU).
  
  
  METHODS
  C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein-derived peptide 1-20 (hIRBP-p). Telmisartan, an AT1-R blocker, was administrated daily by intraperitoneal injection. On day 21 after immunization, the severity of EAU was assessed clinically and histopathologically. With the use of flow cytometry, the activation of draining lymph node (LN) cells was assessed by cell proliferation response against hIRBP-p and by the number of CD44(high) activated CD4(+) T cells present. In addition, mRNA expression of ICAM-1, MCP-1, and IFN-gamma in the eye was analyzed by reverse-transcriptase PCR, and the number of retinal adherent leukocytes was counted by retinal perfusion labeling.
  
  
  RESULTS
  Telmisartan significantly suppressed EAU clinically and histopathologically. Intraocular mRNA expression of ICAM-1 and MCP-1 was downregulated, and the retinal adherent leukocyte counts were significantly decreased in telmisartan-treated mice compared with vehicle-treated mice. LN cell proliferative responses against hIRBP-p and the number of CD44(high)CD4(+) T cells were remarkably reduced in telmisartan-treated mice.
  
  
  CONCLUSIONS
  Systemic administration of telmisartan significantly suppressed EAU by the inhibition of antigen-specific T-cell activation in the LNs and of leukocyte adhesion in the retina. These results indicate that telmisartan may be a novel therapeutic regimen for patients with endogenous uveitis.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D005136:Eye Proteins; D005260:Female; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012173:Retinitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D000077333:Telmisartan; D014605:Uveitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D018932:Chemokine CCL2; D016207:Cytokines; D005136:Eye Proteins; D018799:Intercellular Adhesion Molecule-1; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D000077333:Telmisartan; D000099214:Retinol-Binding Proteins, Interstitial; C491768:Ccl2 protein, mouse; C090509:Icam1 protein, mouse