Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated.


OBJECTIVE
This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment.


METHODS
We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured.


RESULTS
SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012).


CONCLUSIONS
Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.
Furukawa
Hirotoshi
H
Department of Dermatology, School of Medicine, Fukushima Medical University, Hikarigaoka-1, Fukushima 960-1295, Japan. jabbrwsh@fmu.ac.jp
Takahashi
Masanobu
M
Nakamura
Koichiro
K
Kaneko
Fumio
F
D000328:Adult; D000485:Allergens; D002478:Cells, Cultured; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000097:blood*; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D003990:Dibenzoxepins / Q000008:administration & dosage*; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008297:Male; D000069605:Olopatadine Hydrochloride; D039981:Pyroglyphidae / Q000276:immunology
D000485:Allergens; C106230:CCL17 protein, human; C515482:CCL22 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D020382:Interleukin-18; D018664:Interleukin-12; D000069605:Olopatadine Hydrochloride; D007371:Interferon-gamma