Antihistaminic drug olopatadine downmodulates T cell chemotaxis toward CCL17 in patients with atopic dermatitis

摘要

Olopatadine hydrochloride (OLP) is an antihistaminic drugwith selective histamine H1 receptor antagonist activity.1 OLPhas inhibitory effects on the production of various chemical mediators and cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor-a (TNF-a).2,3 It inhibits TNF-a release from humanconjunctival mast cells, and consequently decreases CD54 expression on the cells.3 In the skin, the ability of Langerhans cells (LCs),epidermal antigen-presenting dendritic cells (DCs), to presenthapten to T cells is reduced by OLP with decreased expression ofmajor histocompatibility complex class II and co-stimulatory molecules.4 Furthermore, OLP downmodulates CCL17/TARC production by LCs as well as keratinocytes (KCs), as OLP at aconcentration of 106 or 105 mol/L suppresses the IFN-g/TNF-aaugmented production of CCL17 from HaCaT cells and the mRNAexpression of CCL17 and CCL22 in mature bone marrow DCs, amimicry of pure LCs.5 More recently, OLP was reported to decreasetissue IL-31 and thymic stromal lymphopoietin levels in an atopicdermatitis (AD) mouse model.6,7 An in vivo study also showeddecreased serum levels of CCL17 and CCL22 in AD patients aftertreatment with OLP.8 These findings suggest that OLP downmodulates Th2-mediated skin inflammation at least in part by interfering with the antigen-presenting and chemokine-producingabilities of DCs. However, it remains to be elucidated whetherOLP directly regulate the action of Th2 cells. In this study, wethus studied the effect of OLP on T cell chemotactic activity towardthe Th2 chemokine, CCL17.