Effects of olopatadine hydrochloride, an antihistamine drug, on skin inflammation induced by repeated topical application of oxazolone in mice.
BACKGROUND
Olopatadine hydrochloride (olopatadine) is one of the second-generation antihistamines, which is prescribed for allergic disorders such as rhinitis, urticaria and eczema dermatitis.


OBJECTIVE
To investigate the possible anti-inflammatory effect of olopatadine on the chronic contact hypersensitivity response to repeated topical application of oxazolone in mice.


METHODS
The preventive and therapeutic effects of oral olopatadine were quantified by measurements of ear swelling, cytokine protein and mRNA expression in the ear lesion, and were compared with those of topical betamethasone 17-valerate (betamethasone).


RESULTS
The ear receiving repeated applications of oxazolone exhibited erythema, oedema and abrasion. Both preventive and therapeutic administration of olopatadine (10 mg kg(-1) day(-1)) significantly inhibited the ear swelling and the increased production of interleukin (IL)-4, IL-1beta, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor. In the histopathological analysis, olopatadine ameliorated epidermal hyperplasia and infiltration of inflammatory cells. Consistent with these results, olopatadine significantly reduced the increased expression of interferon-gamma and IL-4 mRNA. Although betamethasone (0.012 mg ear(-1) day(-1)) showed similar activities to olopatadine against these responses, it caused atrophy of the ear skin.


CONCLUSIONS
These results indicate that olopatadine is an antihistamine agent having inhibitory activities against chronic inflammatory dermatitis, possibly resulting from its diminishing effect on elevated cytokines.
Tamura
T
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co. Ltd, 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. tadafumi.tamura@kyowa.co.jp
Matsubara
M
M
Takada
C
C
Hasegawa
K
K
Suzuki
K
K
Ohmori
K
K
Karasawa
A
A
D000276:Adjuvants, Immunologic; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D003990:Dibenzoxepins / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D039563:Histamine H1 Antagonists, Non-Sedating / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000096:biosynthesis; D000069605:Olopatadine Hydrochloride; D010081:Oxazolone; D012333:RNA, Messenger / Q000235:genetics
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D003990:Dibenzoxepins; D039563:Histamine H1 Antagonists, Non-Sedating; D012333:RNA, Messenger; D010081:Oxazolone; D000069605:Olopatadine Hydrochloride; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020932:Nerve Growth Factor