title: Repeated application of glucocorticoids exacerbate pruritus via inhibition of prostaglandin D2 production of mast cells in a murine model of allergic contact dermatitis.
abstract: Rebound is known to occur most typically when topical glucocorticoids are abruptly discontinued; however, its frequency and severity are poorly characterized. We previously created a novel murine model of topical glucocorticoid-induced pruritus; however, the mechanism underlying pruritus in this model has not been elucidated. Using this murine model, we aimed to determine the cause of augmentation of pruritus with a focus on the production of prostaglandin (PG) D(2). BALB/c mice with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) were treated topically with dexamethasone for 5 weeks immediately after the elicitation of dermatitis and after ear-swelling and scratching behavior were measured. RBL-2H3 mast cells were used to investigate the effect of dexamethasone on degranulation or PGD(2) production in IgE/antigen-stimulated mast cells. The scratching behavior induced by TNCB was augmented by topical application of dexamethasone, but dexamethasone did not have any effect on scratching bouts in mice that had not been treated with TNCB. Topical dexamethasone reduced the PGD(2) level, which increase in TNCB-treated mice, to the baseline level. Moreover, dexamethasone significantly decreased the PGD(2) production in IgE/antigen-stimulated RBL-2H3 mast cells; however, the same concentration of dexamethasone did not have any effect on the degranulation of stimulated mast cells. Topical glucocorticoids may exacerbate pruritus in a mouse model of allergic contact dermatitis via inhibition of PGD(2) production in antigen-mediated activated mast cells in the skin.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yamaura
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Doi
authors.forename: Eriko
authors.initials: E
authors.lastname: Suwa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017449:Dermatitis, Allergic Contact; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011537:Pruritus / Q000139:chemically induced*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D015230:Prostaglandin D2; D010853:Picryl Chloride