Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: Implications for anti-inflammatory activity of antihistamines

Background: Desloratadine is an H₁-histamine antagonist which possesses additional anti-inflammatory properties through inhibition of leukocyte activation and reduction of ICAM-1 expression on mucosal epithelial cells. So far no studies have addressed the potential anti-inflammatory activities of desloratadine and loratadine on skin keratinocytes. Objective: In this study the capacity of desloratadine and loratadine to counteract human keratinocyte activation by interferon-γ (IFN-γ) was analyzed. In particular, the chemokine release of kerationcytes and the crosstalk between keratinocytes and lymphocytes were examined. Method: Keratinocyte cultures established from normal skin of healthy donors were activated by IFN-γ in the absence or presence of desloratadine and loratadine, and tested for the release of CCL5/ RANTES, CXCL8/IL-8, CCL17/TARC and CXCL10/IP-10. Furthermore the supernatants of differentially stimulated keratinocytes were used for migration studies of human neutrophils, eosinophils and polarized Th1/Th2 clones. Results: Desloratadine and loratadine inhibited the constitutive and IFN-γ-induced release of CCL5, CXCL8 and CXCL10 from keratinocytes, while the low release of CCL17 remained unchanged. Furthermore the crosstalk between lymphocytes and keratinocytes was blocked as shown by a reduced capacity of desloratadine/loratadine-stimulated keratinocytes to attract human neutrophils, eosinophils and T cells. Conclusions: The results indicate that desloratadine has the capacity to block the IFN-γ-induced activation of keratinocytes, and that it can thus exert important regulatory effects on cell-mediated immune responses in the skin. The rather high doses required for these effects argue for a topical application when trying to use desloratadine in epidermal inflammatory conditions.