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Keywords:

  • cytokines;
  • human mast cells;
  • seasonal allergic conjunctivitis

Summary

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 FcɛRI, 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/106 cells; P<0.05). Pre-treatment by all drugs significantly reduced histamine and TNF-α, whereas IL-5, IL-8, IL-10 and TNF-β profiles were differentially decreased. For conjunctival biopsy-derived cultures (n=11), FcɛR1 stimulation increased histamine, TNF-α, TNF-β, 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).

Conclusion 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.