Eosinophil recruiting chemokines are down-regulated in peripheral blood mononuclear cells of allergic patients treated with deflazacort or desloratadine.
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.
Di Sciascio
M B
MB
Clinical Pathology Unit, Colle dell'Ara University Hospital, Chieti, Italy.
Vianale
G
G
Verna
N
N
Petrarca
C
C
Perrone
A
A
Toniato
E
E
Muraro
R
R
Conti
P
P
Di Gioacchino
M
M
D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002469:Cell Separation; D018925:Chemokines / Q000096:biosynthesis*; D003720:Densitometry; D015536:Down-Regulation / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000378:metabolism*; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D023282:Nuclease Protection Assays; D032403:Parietaria / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011282:Pregnenediones / Q000494:pharmacology* / Q000627:therapeutic use; D012129:Respiratory Function Tests; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D018925:Chemokines; D006634:Histamine H1 Antagonists; D011282:Pregnenediones; D017336:Loratadine; C121345:desloratadine; C021988:deflazacort; D000420:Albuterol