Levocetirizine Inhibits Migration of Immune Cells to Lymph Nodes and Induces Treg Cells in a Murine Type I Allergic Conjunctivitis Model

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.

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)A₄ 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.

OVA exposure induced AC in the animal model indicated by increased expression of LXA₄, TNF-α and TGF-β. Levocetirizine treatment (0.01–0.02% v/w) reduced LXA₄ 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.

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.