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-gamma (IFN-gamma) was analyzed. In particular, the chemokine release of kerationcytes and the crosstalk between keratinocytes and lymphocytes were examined.


METHODS
Keratinocyte cultures established from normal skin of healthy donors were activated by IFN-gamma 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-gamma-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-gamma-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.
Traidl-Hoffmann
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Division of Environmental Dermatology and Allergy GSF/TUM, ZAUM--Center for Allergy and Environment, Munich, Germany. Claudia.Traidl-Hoffmann@lrz.tum.de
Münster
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Ring
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Behrendt
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D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D006634:Histamine H1 Antagonists; D017336:Loratadine; D007371:Interferon-gamma; C121345:desloratadine