Levocetirizine Modulates Lymphocyte Activation in Patients With Allergic Rhinitis

Mahmoud, Fadia; Arifhodžić, Nermina; Haines, David; Novotney, Ladislav

doi:10.1254/jphs.08037fp

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…4 ). Treatment with Levocetirizine 0.02% for 72 h reduced the proportion of CD4 + /CD25 + cells, as previously described [19] (data not shown) and increased the differentiation of CD4 + /CD25 + cells to Treg cells.…”

Section: Resultssupporting

confidence: 86%

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

García-Zepeda

Estrada-Muñiz²,

Elizondo³

et al. 2012

TOOPHTJ

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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.

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Section: Resultssupporting

confidence: 86%

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

García-Zepeda

Estrada-Muñiz²,

Elizondo³

et al. 2012

TOOPHTJ

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“…It also inhibits migration inhibitory factor (MIF)(18) as well as interleukin 8 (IL‐8) and leukotriene B4 (LTB4) production and induces the production of PGE2, a suppressor of antigen presentation and major histocompatibility complex (MHC) class II expression, from monocyte/macrophages (19), reduces the chemotaxis of monocytes and T lymphocytes (20). Moreover CTZ and its parent compound levocetirizine are reported to modulate the activation of T cells and their production of pro‐inflammatory cytokines (21,22); (iii) CTZ reduces the number of tryptase‐positive MC in inflammation sites (13). MC, increased in their number and activation state in LP (4,5) and in LPP, as we have shown (FIG.…”

Section: Discussionmentioning

confidence: 99%

THERAPEUTIC HOTLINE: Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris - an open-label clinical trial

D’Ovidio¹,

Rossi

2010

Dermatologic Therapy

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Lichen planus is considered a T cell-mediated immunological disease. Even mast cells may contribute to the pathogenesis of the disease. Keratinocytes of the basal layer of the skin and/or the hair follicle may represent the "target/victim" of an immune aggression, determining the destruction of the hair follicle and thus scarring alopecia. Therefore, there is a compelling urgency for effective treatment of this potentially disfiguring dermatosis. Our data provide a further therapeutic opportunity: the use of an antihistaminic drug--cetirizine (CTZ)--in an "anti-inflammatory" regimen. We propose the use of CTZ at the dosage of 30 mg/daily. Twenty-one patients affected by lichen planus pilaris (LPP) of the scalp have been treated. Topical application of steroids has been coadministered in all cases during the therapy. Clinical effects, in the sense of stabilization with cessation of the inflammation (erythema, follicular hyperkeratosis, loss of anagen hair), were achieved in all patients but three. One patient developed cardiac arrhythmia after 3 months of successful treatment and dropped out. Our cases indicate that a combined therapy of topical steroid with CTZ can be a safe and effective choice even in severe cases of lichen planus pilaris, so often refractory to the therapy.

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“…12,14 Evidence of anti-inflammatory effect is conflicting due to variety of measured immunologic parameters, inconsistent results and disconnect from efficacy measures. [31][32][33] Under controlled conditions of an EEU or EEC, anti-histaminic effects of LCZ were seen in wheal-and-flare responses vs. PLA, DSL, and MLK 18-20 although these wheal-and-flare tests may not be the best way to prove clinical efficacy of medications used to treat AR. 64 Eight studies, examining 3230 patients, were included in this review of efficacy and QOL of LCZ in patients with SAR.…”

Section: Discussionmentioning

confidence: 99%

“…No significant change in any of cell populations occurred in PLA group. 32 In a study of patients (n = 30) with SAR given LCZ 5 mg/day, 33 DSL 5 mg/day or PLA for 2 weeks, IL-4 levels were reduced by both LCZ and DSL vs. baseline (P = 0.041 and P = 0.044) while only LCZ reduced IL-8 levels when compared to baseline (P = 0.02). LCZ was found to reduce eosinophil counts compared with DSL and PLA (P = 0.008, P = 0.0002), and DSL also reduced eosinophil counts compared with PLA (P = 0.0007).…”

Section: Immunologic Effectsmentioning

confidence: 99%

Levocetirizine: Review of its Use in the Treatment of Seasonal Allergic Rhinitis

McLaughlin-Middlekauff

Elrod²

2011

Clinical Medicine Reviews in Therapeutics

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Background: Levocetirizine (LCZ), the active R-enantiomer of cetirizine, is a second-generation antihistamine approved for symptom treatment due to seasonal allergic rhinitis (SAR), perennial allergic rhinitis, and chronic idiopathic urticaria in patients $6 months of age. Objective: To review available literature about pharmacokinetics, pharmacodynamics, efficacy, tolerability, quality of life, and pharmacoeconomics of LCZ use in adults and children with SAR. Methods: Databases searched were: MEDLINE, CINAHL Plus with Full Text, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, EMBASE, NHS Economic Evaluation Database, and Database of Abstracts of Reviews of Effectiveness. Search terms included levocetirizine, histamine H 1 antagonists-non-sedating, seasonal allergic rhinitis, pregnancy, quality of life, case reports, cost, and pharmacoeconomics. Relevant article reference lists were also used to obtain additional articles. Results: LCZ exhibits rapid and extensive absorption, high affinity/selectivity for H 1 receptor, and rapid onset and long duration of action. Eight articles assessing clinical efficacy were reviewed. In 4 placebo-controlled studies, LCZ 5 mg/day significantly reduced nasal symptoms in 3 studies and had similar efficacy in 1 study. LCZ was more effective in reducing SAR symptoms vs. desloratadine 5 mg/day but not vs. rupatadine (RUP) 10 mg/day, and RUP was more effective than LCZ in reducing nasal symptoms (P = 0.02). Addition of LCZ 5 mg/day to fluticasone nasal spray therapy improved nasal blockage symptoms only (P , 0.005). Studies investigating anti-inflammatory effects produced inconsistent results. LCZ was not associated with serious adverse events and is generally well tolerated with complaints of somnolence and fatigue; also, there was an increase in febrile seizures in infants. Conclusion: LCZ is an effective and well-tolerated second-generation antihistamine used for the treatment of SAR in adults and children, but its effects on inflammatory markers and performance versus other treatment options require further investigation.

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Levocetirizine Modulates Lymphocyte Activation in Patients With Allergic Rhinitis

Cited by 18 publications

References 40 publications

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

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

THERAPEUTIC HOTLINE: Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris - an open-label clinical trial

Levocetirizine: Review of its Use in the Treatment of Seasonal Allergic Rhinitis

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