Document Detail

Impact of desloratadine and loratadine on the crosstalk between human keratinocytes and leukocytes: Implications for anti-inflammatory activity of antihistamines.
MedLine Citation:
PMID:  16741367     Owner:  NLM     Status:  MEDLINE    
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.
METHOD: 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.
C Traidl-Hoffmann; I Münster; J Ring; H Behrendt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-02
Journal Detail:
Title:  International archives of allergy and immunology     Volume:  140     ISSN:  1018-2438     ISO Abbreviation:  Int. Arch. Allergy Immunol.     Publication Date:  2006  
Date Detail:
Created Date:  2006-07-19     Completed Date:  2006-09-05     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9211652     Medline TA:  Int Arch Allergy Immunol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  315-20     Citation Subset:  IM    
Copyright Information:
Copyright 2006 S. Karger AG, Basel.
Division of Environmental Dermatology and Allergy GSF/TUM, ZAUM--Center for Allergy and Environment, Munich, Germany.
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MeSH Terms
Anti-Inflammatory Agents / pharmacology
Cell Communication / drug effects*,  immunology
Cell Movement / drug effects,  immunology
Chemokine CCL5
Chemokine CXCL10
Chemokines, CC / metabolism
Chemokines, CXC / metabolism
Culture Media, Conditioned / pharmacology
Dose-Response Relationship, Drug
Eosinophils / cytology,  drug effects,  immunology
Histamine H1 Antagonists / pharmacology
Interferon-gamma / pharmacology
Keratinocytes / cytology,  drug effects*,  metabolism
Leukocytes / cytology,  drug effects*,  metabolism
Loratadine / analogs & derivatives*,  pharmacology*
Neutrophils / cytology,  drug effects,  immunology
Th1 Cells / cytology,  drug effects,  immunology
Th2 Cells / cytology,  drug effects,  immunology
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/CCL5 protein, human; 0/CXCL10 protein, human; 0/Chemokine CCL5; 0/Chemokine CXCL10; 0/Chemokines, CC; 0/Chemokines, CXC; 0/Culture Media, Conditioned; 0/Histamine H1 Antagonists; 79794-75-5/Loratadine; 82115-62-6/Interferon-gamma; FVF865388R/desloratadine

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