The Effect of Desloratadine on Eosinophil/Basophil Progenitors and Other Inflammatory Markers in Seasonal Allergic Rhinitis: A Placebo-Controlled Randomized Study

Abstract

Background: Eosinophil/basophil (Eo/B) progenitors fluctuate in the peripheral circulation during seasonal allergen exposure in atopic subjects. Several drugs have been shown to modulate Eo/B progenitor levels in the peripheral blood but, to date, the possible effect of antihistamines on Eo/B progenitors has not been explored. Our objective was to evaluate whether the antihistamine desloratadine (DL) can modulate peripheral blood Eo/B progenitors or other markers of allergic inflammation. Methods: We performed a randomized double-blind placebo-controlled study on the effects of DL on peripheral blood Eo/B progenitors in subjects with symptomatic, seasonal allergic rhinitis during a ragweed pollen season. Forty-five subjects were randomized to treatment for 4 weeks with DL 20 mg daily or placebo. Results: The expected fall in the number of Eo/B progenitors from baseline to 2 weeks of treatment was seen in the placebo group [median drop of 1.0 colony-forming unit (CFU)/10⁶ cells], and was greater than in the DL group (median drop of 0.0 CFU/10⁶ cells) (p = 0.013). The change in histamine concentration per colony from baseline to 2 weeks of treatment was lower in the DL group (median decrease of 6.1 pg/colony) compared to placebo (median increase of 1.8 pg/colony) (p = 0.01). An increase in the nasal lavage eotaxin concentration from baseline to 4 weeks of treatment was statistically significant in the placebo group but not in the DL group. Eo/B CFU were not affected by varyingin vitro concentrations of DL. Conclusion: These results suggest that DL can modulate aspects of allergic inflammation in vivo through mechanisms other than simple blockade of H₁ histamine receptors.

Subcutaneous immunotherapy and pharmacotherapy in seasonal allergic rhinitis: A comparison based on meta-analyses

“…We examined 6 trials, which included 525 subjects receiving desloratadine and 530 receiving placebo (see Table E1 in this article's Online Repository at www.jacionline.org). [31][32][33][34][35] The RCI ranged from 29.0% 31 to 235.6%, 33 its weighted mean value was 212.0% (SD, 5.1%; Fig 2, A), and its median value was 211.3%. The ES of individual studies, expressed as the SMD, 8 ranged from 24.28 34 to 20.17, 32 and its overall value was 21.00 (95% CI, 21.68 to 20.32; Fig 2, B).…”

Bone marrow progenitors in inflammation and repair: new vistas in respiratory biology and pathophysiology

“…continual, daily) exposure [55][56][57], with numbers rising again post-seasonally. This has led to the hypothesis of a high-turnover state of these progenitors, with increased trafficking to tissues and their differentiation in situ.…”

“…Circulating Eo/B CFU rise and are then restored to baseline or lower with reinstitution of disease-controlling inhaled therapy, suggesting that progenitor fluctuations contribute to tissue inflammation, and are responsive to tissue signals as well as to topical corticosteroid therapy [57][58][59]. This view is strengthened by the following findings.…”

In situ hematopoiesis: a regulator of TH2 cytokine-mediated immunity and inflammation at mucosal surfaces

“…The first studies to provide indirect evidence that progenitor cells may indeed traffic from the bone marrow to inflamed tissues were performed in subjects with allergic rhinitis. [56][57][58] A series of studies reported a significant elevation of eosinophil-basophil (Eo/B) progenitors before seasonal allergen exposure, followed by rapid reductions in the number of circulating progenitors in subjects during the season as they developed symptoms of rhinitis ( Figure 2). This, in turn, was followed by a rebound back to basal (high circulating) levels at the end of the season (Figure 2).…”