Synergetic Effects of Prednisolone and Olopatadine on Atopic Dermatitis Model of Hairless Mice

Abstract

We investigated the synergetic effects of glucocorticoid and histamine H1 receptor antagonists on an atopic dermatitis model. Hairless mice were used in this study and an atopic dermatitis model was made by repeated application of 2,4,6-trinitrochlorobenzene. The effects of glucocorticoid, histamine H1 receptor antagonists, and the simultaneous use of these drugs were investigated by measuring scratching behavior, skin symptoms and nerve growth factor (NGF) in the skin. Topical application of prednisolone significantly inhibited scratching behavior, skin symptoms and NGF contents in the skin by repeated application. Olopatadine also showed a significant effect on scratching behavior and NGF contents in the skin, whereas chlorpheniramine showed no significant inhibitory effect on these indices. Furthermore, the combined use of prednisolone and olopatadine potentiated the inhibition of scratching behavior, skin symptoms, and NGF in the skin. From these findings, olopatadine potentiated the inhibitory effect of prednisolone on the symptoms of atopic dermatitis by inhibiting NGF.

Current Knowledge and Perspectives on Histamine H1and H2Receptor Pharmacology: Functional Selectivity, Receptor Crosstalk, and Repositioning of Classic Histaminergic Ligands

“…In support of this hypothesis, the antihistamine olopatadine was shown in vivo to enhance prednisolone inhibition of scratching and skin symptoms in an atopic dermatitis murine model (Kagawa et al, 2010). Likewise, H 1 R blocker azelastine reduced the frequency of administration of inhaled corticosteroids without loss of pulmonary function in a clinical trial with patients with chronic asthma (Busse et al, 1996).…”

Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

“…A study from 2011 showed that the combination of both drugs is the most widely-used option in routine clinical practice to treat all types of AR 2 , and three patents have been recently granted to formulations containing the antihistamine azelastine with the synthetic corticosteroids mometasone furoate, ciclesonide and fluticasone propionate 3 . Likewise, concerning AD, the synergistic effects of glucocorticoids and antihistamines have been evaluated in an animal model, where olopatadine potentiated the inhibitory effect of prednisolone on the relief of the inflammatory symptoms leading to the conclusion that this drug combination is useful to treat AD, although the mechanism underlying the synergism was not investigated 41 .…”

Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice

“…However, the role of NO in AD, as well as the role of NO in rhinitis, remains to be elucidated. Recent studies demonstrate the development of a mouse model whose symptoms are similar to those in patients with AD (10–12). These mice show increased scratching and marked elevation of immunoglobulin E (IgE) in plasma, particularly when challenged with allergens.…”