J T Schroeder1, R P Schleimer, L M Lichtenstein, W Kreutner. 1. The Johns Hopkins Asthma and Allergy Center, Department of Medicine, Division of Clinical Immunology, Johns Hopkins University School of, Medicine, Baltimore, Maryland 21224, USA. schray@mail.jhmi.edu
Abstract
BACKGROUND: Desloratadine is a non-sedating, clinically effective, anti-allergic therapy that has been shown to exhibit anti-inflammatory properties that extend beyond its ability to antagonize histamine at H(1)-receptor sites. This latter effect has been shown in vitro to be both IgE-dependent and -independent. OBJECTIVE: In this study, we addressed the ability of desloratadine to inhibit the in vitro generation of interleukin (IL)-4 and IL-13 from human basophils while concurrently comparing its efficacy in preventing mediator release by these cells. METHODS: Basophil-enriched suspensions were treated with various concentrations of desloratadine for 15 min before stimulating with either anti-IgE antibody, calcium ionophore, IL-3 or phorbol ester. Histamine (fluorimetry), LTC(4) (RIA) and IL-4 (ELISA) were all assayed using the same 4-h culture supernatants. IL-13 (ELISA) was measured in supernatants harvested after 20 h incubation. IL-4 mRNA expression (dilutional RT-PCR) was also examined. RESULTS: Desloratadine was found to be nearly six-seven times more potent in preventing the secretion of IL-4 and IL-13 induced by anti-IgE than it was at inhibiting the release of histamine and LTC(4). These cytokines were equally inhibited by desloratadine following activation with ionomycin despite the lack of an effect on the histamine induced with ionomycin. Desloratadine had a lesser effect regarding inhibition of the IL-13 secreted in response to IL-3 and PMA. There was no evidence that desloratadine mediated its inhibitory effects by causing decreased cell viability. Finally, IL-4 mRNA accumulation was remarkably inhibited, by as much as 80%, following pretreatment with desloratadine. CONCLUSION: While capable of inhibiting histamine and LTC(4) release by human basophils, desloratadine is more effective at targeting the signals regulating IL-4 and IL-13 generation in these cells. This inhibitory effect on cytokine generation provides additional evidence that this antihistamine exerts anti-inflammatory properties.
BACKGROUND:Desloratadine is a non-sedating, clinically effective, anti-allergic therapy that has been shown to exhibit anti-inflammatory properties that extend beyond its ability to antagonize histamine at H(1)-receptor sites. This latter effect has been shown in vitro to be both IgE-dependent and -independent. OBJECTIVE: In this study, we addressed the ability of desloratadine to inhibit the in vitro generation of interleukin (IL)-4 and IL-13 from human basophils while concurrently comparing its efficacy in preventing mediator release by these cells. METHODS: Basophil-enriched suspensions were treated with various concentrations of desloratadine for 15 min before stimulating with either anti-IgE antibody, calcium ionophore, IL-3 or phorbol ester. Histamine (fluorimetry), LTC(4) (RIA) and IL-4 (ELISA) were all assayed using the same 4-h culture supernatants. IL-13 (ELISA) was measured in supernatants harvested after 20 h incubation. IL-4 mRNA expression (dilutional RT-PCR) was also examined. RESULTS:Desloratadine was found to be nearly six-seven times more potent in preventing the secretion of IL-4 and IL-13 induced by anti-IgE than it was at inhibiting the release of histamine and LTC(4). These cytokines were equally inhibited by desloratadine following activation with ionomycin despite the lack of an effect on the histamine induced with ionomycin. Desloratadine had a lesser effect regarding inhibition of the IL-13 secreted in response to IL-3 and PMA. There was no evidence that desloratadine mediated its inhibitory effects by causing decreased cell viability. Finally, IL-4 mRNA accumulation was remarkably inhibited, by as much as 80%, following pretreatment with desloratadine. CONCLUSION: While capable of inhibiting histamine and LTC(4) release by human basophils, desloratadine is more effective at targeting the signals regulating IL-4 and IL-13 generation in these cells. This inhibitory effect on cytokine generation provides additional evidence that this antihistamine exerts anti-inflammatory properties.
Authors: Paul J Bryce; Clinton B Mathias; Krista L Harrison; Takeshi Watanabe; Raif S Geha; Hans C Oettgen Journal: J Clin Invest Date: 2006-05-04 Impact factor: 14.808