Olopatadine Ameliorates Rat Experimental Cutaneous Inflammation by Improving Skin Barrier Function

Abstract

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.

Olopatadine Hydrochloride Improves Dermatitis Score and Inhibits Scratch Behavior in NC/Nga Mice

“…Based on this result, it might be speculated that oral administration of olopatadine might affect keratinocyte homeostasis. This phenomenon was also found previously regarding the olopatadine-induced improvement of skin barrier function [34]. Keratinocytes have been considered as an immunocompetent cell type for the production of cytokines or other biological substances [39].…”

“…Previous reports provided evidence for the pleiotropic effects of olopatadine: amelioration of the damaged skin barrier function [34], stabilization of mast cells [35], inhibition of monocyte migration [36], and improvement of inflammation and scratch behavior in oxazolone-evoked chronic dermatitis [28,29]. Of course, the therapeutic effects of olopatadine (reduced inflammatory cell infiltrates, cytokines and histamine) might result from the complex combination of these events.…”

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

“…Moisturizers have less anti-inflammatory activity than PPARα activators, and while topical calcineurin inhibitors display significant anti-inflammatory effects, they compromise both epidermal permeability-barrier functions and antimicrobial barrier function in mice (Kim et al ., 2009). The oral administration of olopatadine hydrochloride has a positive effect on permeability barrier homeostasis and inflammation (Amano et al ., 2007; Tamura et al ., 2008), an observation that is consistent with the known ability of antihistamines (H1 and H2 blockers) to improve barrier function (Ashida et al ., 2001). However, it remains to be determined whether topical administration of olopatadine hydrochloride would also be effective for the treatment of AD, and in addition, it is unclear whether they can prevent the emergence of GC-related side effects.…”

Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis?

“…Importantly, none of the FDA-approved antihistamines antagonize H3R or H4R at standard dosing regimens. In an epicutaneous allergen challenge murine AD model, treatment with the selective H1R antihistamine, olopatadine, not only suppressed inflammation and scratching by inhibiting cytokine/chemokine production (e.g., IL-31, TSLP, TARC) but also improved the skin barrier function [65,66,67,68,69]. Olopatadine has inhibitory effects on the release of inflammatory mediators (e.g., histamine, leukotriene, thromboxane, and tachykinins), which could explain these broad anti-allergic properties [70].…”