title: DP2 (CRTh2) antagonism reduces ocular inflammation induced by allergen challenge and respiratory syncytial virus.
abstract: BACKGROUND
  Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D(2) (PGD(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD(2), therefore, may be involved in both early and late phase reactions in response to allergen challenge.
  
  
  METHODS
  Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection.
  
  
  RESULTS
  Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production.
  
  
  CONCLUSIONS
  These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis.
authors: Amira Pharmaceuticals, San Diego, Calif., USA. kstebbins@inceptionsci.com
authors: Karin J
authors: KJ
authors: Stebbins
authors: Alexander R
authors: AR
authors: Broadhead
authors: Alla
authors: A
authors: Musiyenko
authors: Sailen
authors: S
authors: Barik
authors: Jill M
authors: JM
authors: Scott
authors: Yen P
authors: YP
authors: Truong
authors: Brian A
authors: BA
authors: Stearns
authors: John H
authors: JH
authors: Hutchinson
authors: Peppi
authors: P
authors: Prasit
authors: Jilly F
authors: JF
authors: Evans
authors: Daniel S
authors: DS
authors: Lorrain
mesh_terms: D000287:Administration, Topical; D000485:Allergens / Q000276:immunology; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003236:Conjunctivitis, Viral / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000276:immunology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001713:Biphenyl Compounds
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D001596:Benzylamines; D015847:Interleukin-4; D010047:Ovalbumin; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C548542:(2'-((cyclopropanecarbonylethylamino)methyl)-6-methoxy-4'-trifluoromethyl-biphenyl-3-yl)acetic acid; D001713:Biphenyl Compounds; C036293:prostaglandin D2 receptor