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

Int Arch Allergy Immunol. 2006;140(4):315-20. doi: 10.1159/000093709. Epub 2006 Jun 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Cell Communication / drug effects*
  • Cell Communication / immunology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Chemokine CCL5
  • Chemokine CXCL10
  • Chemokines, CC / metabolism
  • Chemokines, CXC / metabolism
  • Culture Media, Conditioned / pharmacology
  • Dose-Response Relationship, Drug
  • Eosinophils / cytology
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Histamine H1 Antagonists / pharmacology
  • Humans
  • Interferon-gamma / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Leukocytes / cytology
  • Leukocytes / drug effects*
  • Leukocytes / metabolism
  • Loratadine / analogs & derivatives*
  • Loratadine / pharmacology*
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Anti-Inflammatory Agents
  • CCL5 protein, human
  • CXCL10 protein, human
  • Chemokine CCL5
  • Chemokine CXCL10
  • Chemokines, CC
  • Chemokines, CXC
  • Culture Media, Conditioned
  • Histamine H1 Antagonists
  • Loratadine
  • Interferon-gamma
  • desloratadine