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Randomized Controlled Trial
. 2010 Feb 9;11(1):17.
doi: 10.1186/1465-9921-11-17.

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

Lennart Greiff  1 , Cecilia Ahlström-Emanuelsson, Ash Bahl, Thomas Bengtsson, Kerstin Dahlström, Jonas Erjefält, Henrik Widegren, Morgan Andersson
Affiliations
Randomized Controlled Trial

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

Lennart Greiff et al. Respir Res. .

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.

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Figures

Figure 1
Figure 1
A. Tryptase (A), ECP (B), and α2-macroglobulin (C) in lavages obtained at baseline (before allergen challenge) and in corresponding lavages late into the allergen challenge series (prior to bradykinin challenge) in the placebo run (median values with interquartile ranges). The allergen challenge series produced an inflammatory response characterized by increased mast cell and eosinophil activity as well as by plasma exudation. (*Denotes p < 0.05, ***denotes p < 0.001, and ****denotes p < 0.0001.)
Figure 2
Figure 2
α2-Macroglobulin in lavages obtained at baseline and late into the allergen challenge series prior to and after bradykinin challenge in the placebo run (median values with interquartile ranges). Bradykinin produced plasma exudation, a process that may facilitate luminal entry of tissue solutes including tryptase and ECP. (****Denotes p < 0.0001.)
Figure 3
Figure 3
Tryptase (A), ECP (B), and α2-macroglobulin (C) in lavages obtained late into the allergen challenge series prior to and after bradykinin challenge (median values with interquartile ranges). AZD3778 reduced the levels of ECP in lavages obtained prior to as well as after bradykinin challenge (c.f. placebo). Whereas this change reached borderline statistical significance prior to bradykinin challenge (p = 0.08), it was statistically significant after the challenge. In contrast to AZD3778, loratadine failed to reduce the levels of ECP (c.f. placebo). Furthermore, ECP recorded at AZD3778 treatment were significantly lower compared to at treatment with loratadine. The treatments all failed to reduce the lavage fluid levels of tryptase and α2-macroglobulin (*Denotes p < 0.05 and ***denotes p < 0.001.)
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References

    1. Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med. 1996;183:2437–2448. doi: 10.1084/jem.183.6.2437. - DOI - PMC - PubMed
    1. Sallusto F, Mackay CR, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T-helper 2 cells. Science. 1997;227:2005–2007. doi: 10.1126/science.277.5334.2005. - DOI - PubMed
    1. Uguccioni M, Mackay CR, Ochenberger B, Loetscher P, Rhis S, LaRosa GJ, Rao P, Ponath PD, Baggiolini M, Dahinden CA. High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest. 1997;100:1137–1143. doi: 10.1172/JCI119624. - DOI - PMC - PubMed
    1. Ochi H, Hirani WM, Yuan Q, Friend DS, Austen KF, Boyce JA. T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro. J Exp Med. 1999;190:267–280. doi: 10.1084/jem.190.2.267. - DOI - PMC - PubMed
    1. Joubert P, Lajoie-Kadoch S, Labonte I, Gounni AS, Maghni K, Wellemans V, Chakir J, Laviolette M, Hamid Q, Lamkhioued B. CCR3 expression and function in asthmatic airway smooth muscle cells. J Immunol. 2005;175:2702–2708. - PubMed

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