title: Ocular anti-allergic compounds selectively inhibit human mast cell cytokines in vitro and conjunctival cell infiltration in vivo.
abstract: BACKGROUND
  Conjunctival mast cells (MCs) are important effector cells in seasonal allergic conjunctivitis, via histamine and cytokine secretion. Several new anti-allergic eye drops stabilize MCs and block histamine receptors, but their anti-inflammatory effects are unclear.
  
  
  OBJECTIVE
  Anti-allergic drugs were compared for their anti-inflammatory effects in an in vitro model of human MC activation and in an experimental murine model of allergic conjunctivitis.
  
  
  METHODS
  Human cord blood stem cell-derived (CBMC) and conjunctival biopsy-derived MCs were stimulated via FcepsilonRI, degranulation and histamine release were assayed at 1 h and cytokine secretion at 24 h using multiplex arrays. Mice sensitized to short ragweed pollen were given anti-allergics topically before allergen challenge, and conjunctival immuno-staining was performed at 24 h.
  
  
  RESULTS
  After a 1 h stimulation, 80% of the CBMC had degranulated and secreted histamine (27.9+/-4.7 ng/10(6) cells; P<0.05). Pre-treatment by all drugs significantly reduced histamine and TNF-alpha, whereas IL-5, IL-8, IL-10 and TNF-beta profiles were differentially decreased. For conjunctival biopsy-derived cultures (n=11), FcepsilonR1 stimulation increased histamine, TNF-alpha, TNF-beta, IL-5 and IL-8 levels and the production of IL-5, IL-6 (P<0.05), histamine and IL-8 (P<0.01) was inhibited by epinastine. In vivo, epinastine and olopatadine pre-treatment significantly reduced the clinical scores and eosinophil numbers (n=6; P<0.05) while epinastine also reduced neutrophils (P<0.02).
  
  
  CONCLUSIONS
  Differential effects on MC cytokine inhibition were observed, with epinastine inhibiting MC secretion of IL-5, IL-8, IL-10 and conjunctival neutrophil infiltration. The anti-allergic drugs have anti-histamine and mast-cell stabilizing properties but might differ in clinical improvement depending on the individual and the cytokines involved.
authors: Institute of Ophthalmology, UCL, London, UK.
authors: Grazyna
authors: G
authors: Galatowicz
authors: Yetunde
authors: Y
authors: Ajayi
authors: Michael E
authors: ME
authors: Stern
authors: Virginia L
authors: VL
authors: Calder
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology; D003233:Conjunctivitis, Allergic / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology / Q000627:therapeutic use; D003990:Dibenzoxepins / Q000494:pharmacology / Q000627:therapeutic use; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017835:Nedocromil / Q000494:pharmacology / Q000627:therapeutic use; D009504:Neutrophils / Q000473:pathology; D000069605:Olopatadine Hydrochloride; D011058:Pollen / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D017455:Receptors, IgE / Q000819:agonists; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D003984:Dibenzazepines; D003990:Dibenzoxepins; D007093:Imidazoles; D017455:Receptors, IgE; D017835:Nedocromil; D000069605:Olopatadine Hydrochloride; D019009:Proto-Oncogene Proteins c-kit; C053090:epinastine