Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

Tamura, Tadafumi; Matsubara, Masahiro; Hasegawa, Kazuhide; Ohmori, Kenji; Karasawa, Akira

doi:10.1111/j.1365-2222.2005.02147.x

Cited by 18 publications

(13 citation statements)

References 28 publications

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“…Upon withdrawal of topical dexamethasone, the mice might have been at a stage of exacerbation of ear dermatitis toward the level seen in the TNCB control, and this might have been associated with a marked shift in the cytokine milieu towards a Th2 profile. In addition, the ear thickness exceeded that in the TNCB control after continuous observation for a long period (data not shown), in agreement with previous reports (Inoue et al, 2003;Tamura et al, 2005).…”

Section: Discussionsupporting

confidence: 92%

“…For these reasons it is important to investigate the mechanism of itching after withdrawal of glucocorticoid treatment, and to control it, although the underlying factors responsible still remain unclear. For studies in this field, it is important to select an appropriate animal model, and some such models have been reported to mimic the exacerbation of dermal inflammation, known as the rebound phenomenon, following withdrawal of long-term glucocorticoid therapy in AD patients (Inoue et al, 2003;Tamura et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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A novel animal model of pruritus induced by successive application of glucocorticoid to mouse skin

et al. 2011

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-Topical glucocorticoids are commonly applied for treatment of atopic dermatitis, and are often administered over a long period. However, itching often occurs as a rebound phenomenon after cessation of long-term glucocorticoid application. The present study was an initial trial designed to establish an animal model of glucocorticoid-induced pruritus by topical application of dexamethasone over a long period in mice with contact dermatitis. 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 3 weeks from 2 weeks after the elicitation of dermatitis. The effects of dexamethasone on inflammation and pruritus were evaluated by measurement of ear-swelling and scratching behavior, respectively. Significant enhancement of pruritus was confirmed after chronic application of dexamethasone. The increased frequency of scratching behavior was reduced by withdrawal of dexamethasone. On the other hand, ear-swelling was markedly ameliorated by dexamethasone treatment, but rapidly relapsed after dexamethasone withdrawal. The level of interleukin (IL)-4 mRNA in ear skin and that of IgE in serum were increased in the mice with dermatitis and reduced by dexamethasone treatment. On the other hand, the level of nerve growth factor (NGF) mRNA was slightly increased by dexamethasone treatment and remained high even after its discontinuation. It is anticipated that this novel animal model of glucocorticoid-induced pruritus will be useful for clarifying the mechanisms of the rebound phenomenon induced by chronic treatment with topical glucocorticoids, and for developing a new form of therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

A novel animal model of pruritus induced by successive application of glucocorticoid to mouse skin

et al. 2011

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“…Prior efforts to reduce the adverse effects of topical GC on cutaneous structure and function have involved moisturizers (Cork et al ., 2003; Chamlin et al ., 2002; Wirén et al ., 2009), topical calcineurin inhibitors (Meurer et al ., 2002; Furue et al ., 2004), and an oral antihistamine, olopatadine hydrochloride (Tamura et al ., 2005), both in patients with AD and in murine AD models. However, PPARα ligands, such as Wy14643, could appear to provide a superior choice for the prevention of the adverse effects of topical GC, because PPARα ligands have both anti-inflammatory effects and potent positive effects on cutaneous barrier homeostasis (Sheu et al ., 2002; Komuves et al ., 2000; Fluhr et al ., 2009).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Combined Peroxisome Proliferator-Activated Receptor-α Ligand and Glucocorticoid Therapy in a Murine Model of Atopic Dermatitis

Hatano

Elias

Crumrine

et al. 2011

Journal of Investigative Dermatology

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Although topical glucocorticoids (GCs) display potent anti-inflammatory activity in inflamed skin, they also can exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation, and also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone)-induced, murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced: i) epidermal thinning; ii) reduced expression of involucrin, loricrin and filaggrin; and iii) allowed outside-to-inside penetration of an epicutaneous tracer. While Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical applications of Wy14643 after GC was not only significantly effective comparable to GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD.

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“…Moreover, an exacerbated relapse often occurs after discontinuing the prolonged use of topical steroids [31] . Olopatadine inhibited the rebound phenomenon following discontinuation of the treatment with a topical corticosteroid [32] . Thus, olopatadine may be therapeutically useful in combination with a topical steroid to accelerate the recovery of the skin barrier damaged by using a topical corticosteroid.…”

Section: Discussionmentioning

confidence: 99%

Olopatadine Ameliorates Rat Experimental Cutaneous Inflammation by Improving Skin Barrier Function

et al. 2007

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Olopatadine hydrochloride (olopatadine) is an antiallergic agent with histamine H₁ receptor antagonistic action. We investigated the possible efficacies of olopatadine on the chronic inflammatory dermatitis and the impaired skin barrier functions induced by repeated application of oxazolone in rats. Oxazolone-sensitized rats were challenged with oxazolone applied to the ear every 3 days. Olopatadine was orally administered once daily (1 and 3 mg/kg/day). The effects of the drug were quantified by measurements of ear thickness, levels of cytokines in the lesioned ear and the number of scratching episodes. As parameters of skin barrier function, transepidermal water loss (TEWL) and hyaluronic acid (HA) levels in the lesioned ear were measured. The effect of olopatadine on the production of HA by cultured dermal fibroblasts was also measured. Repeated topical application of oxazolone to rat ears induced local inflammation that was exemplified by swelling. In inflamed ears, the amount of IFNγ increased at both the protein and mRNA level, but IL-4 levels changed minimally. Olopatadine significantly decreased ear swelling and the number of scratching episodes. The drug also significantly inhibited the increase of IFNγ and nerve growth factor production in inflamed ears. Olopatadine significantly inhibited the increase in TEWL and the decrease in HA in lesioned ears. Furthermore, the drug stimulated the production of HA by cultured dermal fibroblasts. These results suggest that olopatadine suppressed inflammation and scratching not only by inhibiting cytokine production, but also by repairing skin barrier function.

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Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

Cited by 18 publications

References 28 publications

A novel animal model of pruritus induced by successive application of glucocorticoid to mouse skin

A novel animal model of pruritus induced by successive application of glucocorticoid to mouse skin

Efficacy of Combined Peroxisome Proliferator-Activated Receptor-α Ligand and Glucocorticoid Therapy in a Murine Model of Atopic Dermatitis

Olopatadine Ameliorates Rat Experimental Cutaneous Inflammation by Improving Skin Barrier Function

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