Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine

• Published in: Clinical and experimental allergy 2001-09, Vol.31 (9), p.1369-1377
• Main Authors: Schroeder, J. T., Schleimer, R. P., Lichtenstein, L. M., Kreutner, W.
• Format: Article
• Language: English
• Subjects: antagonist; basophil; Basophils - drug effects; Basophils - immunology; Basophils - metabolism; Biological and medical sciences; Cell Culture Techniques; cytokine; Cytokines - drug effects; Cytokines - metabolism; desloratadine; Dose-Response Relationship, Drug; Gene Expression - drug effects; H1-receptor; histamine; Histamine and antagonists. Allergy; Histamine H1 Antagonists - pharmacology; Histamine Release - drug effects; Humans; IgE; Immunoglobulin E - drug effects; Immunoglobulin E - immunology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Interleukin-13 - metabolism; Interleukin-4 - genetics; Interleukin-4 - metabolism; leukotriene; Leukotriene C4 - metabolism; Loratadine - analogs & derivatives; Loratadine - pharmacology; Medical sciences; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; Sensitivity and Specificity
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2001.01130.x

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 H1‐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), LTC4 (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 LTC4. 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 LTC4 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.