Effects of a dual CCR3 and H(1)-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

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 H(1)-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 α(2)-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.