Olopatadine ameliorates rat experimental cutaneous inflammation by improving skin barrier function.
Olopatadine hydrochloride (olopatadine) is an antiallergic agent with histamine H(1) 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 IFN gamma 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 IFN gamma 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.
Tamura
Tadafumi
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan. tadafumi.tamura@kyowa.co.jp
Matsubara
Masahiro
M
Amano
Toru
T
Chida
Michihiro
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003990:Dibenzoxepins / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000069605:Olopatadine Hydrochloride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014870:Water Loss, Insensible / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride