Effects of a dual CCR3 and H1-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 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.


BACKGROUND
EudraCT No: 2005-002805-21.
Greiff
Lennart
L
Department of ORL, Head & Neck Surgery, Lund University Hospital, Lund, Sweden. lennart.greiff@skane.se
Ahlström-Emanuelsson
Cecilia
C
Bahl
Ash
A
Bengtsson
Thomas
T
Dahlström
Kerstin
K
Erjefält
Jonas
J
Widegren
Henrik
H
Andersson
Morgan
M
D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D011657:Pulmonary Eosinophilia / Q000150:complications* / Q000188:drug therapy*; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome
C515350:CCR3 protein, human; D006634:Histamine H1 Antagonists; D054397:Receptors, CCR3