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Cetirizine and hydrocortisone differentially regulate ICAM‐1 expression and chemokine release in cultured human keratinocytes
Author(s) -
Cristina Albanesi,
Saveria Pastore,
Emanuele Fanales-Belasio,
Giampiero Girolomoni
Publication year - 1998
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1998.00206.x
Subject(s) - cetirizine , chemokine , mhc class ii , icam 1 , biology , endocrinology , immunology , microbiology and biotechnology , medicine , chemistry , t cell , inflammation , immune system , cell adhesion molecule
Background Cetirizine is a H 1 histamine antagonist which possesses anti‐inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM‐1 expression on mucosal epithelial cells. No studies have addressed the potential anti‐inflammatory activities of cetirizine on skin keratinocytes. Objectives Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNγ. In particular, expression of immuno‐modulatory membrane molecules and chemokine release have been examined. Methods Keratinocyte cultures established from normal skin of healthy donors were activated by IFNγ (100–500 U/mL) in the absence or presence of cetirizine (10 −3 –10 3 μM) or hydrocortisone (10 −3 –10 2 μM), and tested for expression of ICAM‐1, HLA‐DR, MHC class I and CD40 as well as for release of RANTES, IL‐8, macrophage chemotactic protein‐1 (MCP‐1) and granulocyte macrophage‐colony stimulating factor (GM‐CSF). Results Cetirizine at high concentrations (10 2 –10 3 μM) markedly inhibited IFNγ‐induced expression of membrane ICAM‐1, HLA‐DR and up‐regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (10 2 μM) enhanced IFNγ‐induced membrane ICAM‐1, reduced expression of HLA‐DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM‐1 levels in the supernatants of IFNγ‐treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM‐1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP‐1 and RANTES from IFNγ‐stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM‐CSF and IL‐8 release. Conclusions The results indicate that cetirizine has the capacity to block the IFNγ‐induced activation of keratinocytes, and thus can exert important regulatory effects on TH 1 cell‐mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.