title: Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms.
abstract: BACKGROUND
  Nedocromil sodium and levocabastine are widely used for the treatment of ocular allergy, but their mechanisms of action are unclear.
  
  
  OBJECTIVE
  We sought to compare the efficacy and mechanisms of action of nedocromil sodium and levocabastine in reducing conjunctival symptoms after ocular allergen challenge.
  
  
  METHODS
  We performed a double-blind, placebo-controlled study in which 48 subjects were randomized to 3 groups to receive nedocromil sodium (2%), levocabastine (0.05%), or placebo eye drops twice daily for 2 weeks before ocular challenge with 10 microL of ryegrass extract. Symptoms and tear histamine and PGD(2) concentrations were determined before challenge and at 10, 20, 30, 60, 180, and 360 minutes after challenge. Bulbar biopsy specimens were taken at 6 and 24 hours after challenge to assess conjunctival inflammatory cell numbers, adhesion molecule expression, and mast cell-associated IL-4, IL-5, IL-6, IL-13, and TNF-alpha levels.
  
  
  RESULTS
  Both drugs significantly reduced total symptom scores (P <.05) at all times after challenge compared with placebo. Itching, hyperemia, and lacrimation were most affected. Nedocromil sodium treatment reduced tear concentrations of histamine (by 77%) and PGD(2) (by 70%) at 30 minutes after challenge (both P <.05). In biopsy specimens nedocromil sodium reduced the number of 3H4-positive mast cells (purportedly the secreted form of IL-4) by 49% at 6 hours and 59% at 24 hours (both P <.05). Levocabastine reduced intercellular adhesion molecule 1 expression by 52% at 6 hours and 45% at 24 hours (both P <.05).
  
  
  CONCLUSIONS
  Nedocromil sodium and levocabastine both reduced the conjunctival symptoms after ocular allergen challenge but appeared to work by different mechanisms. Nedocromil sodium reduced mast cell function, whereas levocabastine appeared to have primarily antihistaminic actions, although it also reduced the expression of intercellular adhesion molecule 1.
authors.affiliation: Allergy and Inflammation Sciences, Southampton University Medical School, Southampton, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Ahluwalia
authors.forename: D F
authors.initials: DF
authors.lastname: Anderson
authors.forename: S J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: J I
authors.initials: JI
authors.lastname: McGill
authors.forename: M K
authors.initials: MK
authors.lastname: Church
mesh_terms: D000328:Adult; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D003228:Conjunctiva / Q000737:chemistry; D003233:Conjunctivitis, Allergic / Q000188:drug therapy*; D019040:E-Selectin / Q000032:analysis; D005260:Female; D006632:Histamine / Q000032:analysis; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008129:Lolium / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017835:Nedocromil / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D015230:Prostaglandin D2 / Q000032:analysis; D013666:Tears / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D018926:Anti-Allergic Agents; D019040:E-Selectin; D006634:Histamine H1 Antagonists; D010880:Piperidines; D019010:Vascular Cell Adhesion Molecule-1; D017835:Nedocromil; D018799:Intercellular Adhesion Molecule-1; D006632:Histamine; C047340:levocabastine; D015230:Prostaglandin D2