Levocetirizine inhibits migration of immune cells to lymph nodes and induces treg cells in a murine type I allergic conjunctivitis model.

unlabelledBACKGROUND #ENTITYSTARTX00026; PURPOSE: Levocetirizine is a histamine H(1) receptor antagonist. Here, we utilised DO11.10TCR transgenic mice to establish an antigen-specific T cell-dependent allergic conjunctivitis (AC) model to determine the effect of the topical application of an ophthalmic formulation of Levoceritizine as a treatment for AC. EXPERIMENTAL APPROACH: DO11.10 mice (n=6/each) were exposed to ovalbumin (OVA, 50 µg) and treated with a Levocetirizine ophthalmic formulation (0.001-0.02% v/w) or placebo (vehicle) for 24-72 h. Serum, aqueous/vitreous humour and conjunctiva were obtained. Immunoglobulin (Ig)-E, interleukin (IL)-10 and lipoxin (LX)A(4) were determined by ELISA. Levels of tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interferon (IFN)-γ and 18rS expression were measured by RT-PCR. Proportions of total and activated antigen-presenting cells (APC), recruited T lymphocytes (CD4+), activated T lymphocytes (CD25+) and T regulatory cells (Treg) were measured by flow cytometry. KEY

resultsOVA exposure induced AC in the animal model indicated by increased expression of LXA(4), TNF-α and TGF-β. Levocetirizine treatment (0.01-0.02% v/w) reduced LXA(4) in the eye humours. This treatment approach increased systemic IL-10 secretion and reduced TNF-α and TGF-β expression in conjunctiva without changing IFN-γ expression. Levocetirizine reduced APC levels in draining lymph nodes but increased the proportion of total lymphocytes recruited and their differentiation to Treg cells. CONCLUSIONS #ENTITYSTARTX00026; IMPLICATIONS: Levocetirizine effectively reduces the activation and migration of APC to local draining lymph nodes and induces differentiation of Treg cells as one possible mechanism of its anti-inflammatory action.