ORIGINAL ARTICLES
Olopatadine inhibits TNFα release from human conjunctival mast cells

https://doi.org/10.1016/S1081-1206(10)62513-6Get rights and content

Background

Tumor necrosis factor-α (TNFα) release likely plays a crucial role in allergic ocular inflammation via increasing ICAM-1 on epithelial cells and triggering other proinflammatory events. The immediate and prolonged release of TNFα from human conjunctival mast cells in response to allergen challenge is potentially an important target for therapeutic intervention, yet the effect of ocular anti-allergic agents on this process has not been examined. Olopatadine (Patanol) is a clinically effective dual-action ophthalmic anti-allergic agent that has been shown to inhibit mast cell histamine, tryptase, and PGD2 release in vitro and promote decreased H1 receptor binding activity in vitro and functional H1 receptor antagonism in vivo.

Objective

To investigate the effect of olopatadine on TNFα release from anti-IgE antibody challenged purified human conjunctival mast cells.

Methods

Human conjunctival mast cells were purified (>95%) from cadaveric tissues using a procedure combining enzymatic digestion and Percoll gradient centrifugation. These cells were incubated with olopatadine for 30 minutes then challenged with anti-IgE antibody for 90 minutes. Supernatants were analyzed for TNFα.

Results

Purified human conjunctival mast cells responded to anti-IgE antibody challenge with TNFα release in a concentration dependent manner (optimum concentration was 10 μg/mL). Olopatadine pre-incubation resulted in a dose-dependent decrease in anti-IgE antibody mediated TNFα release (IC50 = 13.1 μM). At a concentration of 3 mM olopatadine reduced TNFα release to the level of unchallenged controls.

Conclusion

Olopatadine inhibited anti-IgE antibody-mediated release of TNFα from human conjunctival mast cells. This effect could contribute to the long duration of anti-allergic activity reported for the drug.

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This work was supported in part by Alcon Labs, Fort Worth, TX, an unrestricted grant from The Society to Prevent Blindness and NIH Grant EY12526.

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