RESEARCH ARTICLE


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



Sihomara García-Zepeda1, Elizabet Estrada-Muñiz1, Guillermo Elizondo2, Luis I Terrazas3, Miriam Rodríguez-Sosa3, Juan D Quintana-Hau4, Rubén Tornero-Montaño4, Leopoldo Baiza-Durán4, Libia Vega*, 1
1 Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados- IPN. Av. IPN 2508, San Pedro Zacatenco, México D.F. 07360, México;
2 Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados- IPN. Av. IPN 2508, San Pedro Zacatenco, México D.F. 07360, México;
3 Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México, México;
4 Laboratorios SOPHIA, Guadalajara, Jalisco, México


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© García-Zepeda et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Departamento de Toxicología, CINVESTAV, Av. IPN 2508, San Pedro Zacatenco, México D. F., 07360, México; Tel: +52-55-57473800, Ext. 5472; Fax: +52-55-57473395; E-mail: lvega@cinvestav.mx


Abstract

Background & 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)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.

Key Results:

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.

Conclusions & 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.

Keywords:: Levocetirizine, cytokines, allergic conjunctivitis, antigen-presenting cells.