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Eosinophil recruiting chemokines are down-regulated in peripheral blood mononuclear cells of allergic patients treated with deflazacort or desloratadine.

Abstract
Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophils-basophils activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic-asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, I-309 (CCL1), MCP-1 (CCL2), MIP1-alpha (CCL3), MIP1-beta (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-alpha and MIP1-beta with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.
AuthorsM B Di Sciascio, G Vianale, N Verna, C Petrarca, A Perrone, E Toniato, R Muraro, P Conti, M Di Gioacchino
JournalInternational journal of immunopathology and pharmacology (Int J Immunopathol Pharmacol) 2007 Oct-Dec Vol. 20 Issue 4 Pg. 745-51 ISSN: 0394-6320 [Print] England
PMID18179747 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • Chemokines
  • Histamine H1 Antagonists
  • Pregnenediones
  • Loratadine
  • desloratadine
  • deflazacort
  • Albuterol
Topics
  • Adolescent
  • Adult
  • Albuterol (therapeutic use)
  • Anti-Inflammatory Agents (pharmacology, therapeutic use)
  • Asthma (physiopathology)
  • Bronchodilator Agents (therapeutic use)
  • Cell Separation
  • Chemokines (biosynthesis)
  • Densitometry
  • Down-Regulation (drug effects)
  • Eosinophils (drug effects)
  • Female
  • Gene Expression (drug effects)
  • Histamine H1 Antagonists (pharmacology, therapeutic use)
  • Humans
  • Hypersensitivity (drug therapy, metabolism)
  • Loratadine (analogs & derivatives, pharmacology, therapeutic use)
  • Male
  • Monocytes (drug effects, metabolism)
  • Nuclease Protection Assays
  • Parietaria (immunology)
  • Pollen (immunology)
  • Pregnenediones (pharmacology, therapeutic use)
  • Respiratory Function Tests
  • Rhinitis, Allergic, Seasonal (metabolism)

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