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Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis.

ABSTRACT: BACKGROUND: The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation. OBJECTIVE: To examine whether a dual CCR3 and H1-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis. METHODS: Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and alpha2-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation. RESULTS: Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine. CONCLUSIONS: AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis. TRIAL REGISTRATION: EudraCT No: 2005-002805-21.

SUBMITTER: Greiff L

PROVIDER: S-EPMC2833142 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis.

Greiff Lennart L Ahlström-Emanuelsson Cecilia C Bahl Ash A Bengtsson Thomas T Dahlström Kerstin K Erjefält Jonas J Widegren Henrik H Andersson Morgan M

Respiratory research 20100209

<h4>Background</h4>The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation.<h4>Objective</h4>To examine whether a dual CCR3 and H1-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis.<h4>Methods</h4>Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Sy ...[more]

PMID: 20144207

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Project description:Allergic rhinitis is characterized by a chronic inflammation of nasal mucosa and represents a risk factor for asthma occurrence. H1 antihistamines reduce the symptoms of rhinitis, but some compounds may have anti-inflammatory properties.We evaluated the plasma level of some cytokines in patients with persistent allergic rhinitis (PAR) and their evolution after a 4-week treatment with H1 anti-histamines, as well as the risk of asthma after 1.5 years.Randomized clinical trial.Eighty-five patients with PAR and 30 healthy volunteers were included in the study. The patients with PAR were randomly divided into 2 groups: 41 patients treated with 5 mg/day desloratadine and 44 patients under 5 mg/day levocetirizine for 4 weeks. The clinical and biological evaluations were performed before and after treatment and included rhinitis symptoms and total symptoms score, type of sensitization, and plasmatic levels of total IgE, IL-1?, IL-6, IL-8 and TNF-?.IL-8 and TNF-? were significantly increased in patients with PAR compared to healthy volunteers (5.85 vs 3.12, p<0.001 and 2.32 vs 1.06, p<0.001, respectively). Both H1 antihistamines reduce all symptoms of allergic rhinitis, including nasal congestion and the plasmatic level of IL-1?, IL-6, IL-8 and TNF-?, after 4 weeks of treatment. The reduction of cytokine levels was not influenced by patients' age, sex, duration or severity of rhinitis, or type of sensitization. Levocetirizine has a superior effect compared to desloratadine in reducing the rhinitis symptoms and cytokines' level. Twenty eight (32.9%) of the patients presented asthma symptoms after 1.5 years. The occurrence of asthma was influenced by house dust sensitization (OR-14.6; CI 95% 1.8-116.3; p=0.01), but baseline values of cytokines were not predictive factors for its appearance.Levocetirizine and desloratadine as a prolonged therapy reduce plasmatic levels of some pro-inflammatory cytokines in patients with PAR. Levocetirizine has a better effect on decreasing the symptoms and plasmatic levels of IL-1? and IL-8. (ClinicalTrials. gov Identifier: NCT02507635).POSDRU and University of Medicine and Pharmacy, Iuliu Ha?ieganu, Cluj Napoca.

Dataset Information

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis.

Publications

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis.

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