Ocular anti-allergic compounds selectively inhibit human mast cell cytokines in vitro and conjunctival cell infiltration in vivo.
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.
Galatowicz
Grazyna
G
Institute of Ophthalmology, UCL, London, UK.
Ajayi
Yetunde
Y
Stern
Michael E
ME
Calder
Virginia L
VL
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
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