Research & Development Center, Santen Pharmaceutical Co., Ltd., Ikoma, Nara, Japan.
Biol Pharm Bull. 2010;33(8):1314-8. doi: 10.1248/bpb.33.1314.
We investigated the efficacy of cyclosporine A (CyA) eye drops on ocular symptoms in late phase and delayed-type reactions in guinea pig allergic conjunctivitis models. An emulsion of ovalbumin (OVA) and Freund's complete adjuvant (FCA) was intraperitoneally injected into guinea pigs, and 15% OVA solution was applied topically to the eyes to elicit late phase reactions. Following the early phase reaction, increased scores for hyperemia, swelling, edema, and discharge were detected 6 h after antigen challenge, and CyA eye drops significantly inhibited the increase in scores for edema and discharge, the increase in the number of infiltrating inflammatory cells, and the percentage of eosinophils among polymorphonuclear leukocytes in conjunctival tissue. To induce delayed-type reactions, guinea pigs were sensitized by injecting FCA into the footpad, followed by injections of purified protein derivative into palpebral conjunctivae 24 d later. Increased scores for hyperemia, swelling, and discharge were detected 6 h after the induction of delayed-type allergy, and CyA eye drops significantly inhibited the increase in scores for hyperemia and swelling. In contrast, betamethasone sodium phosphate eye drops showed a tendency to inhibit the symptoms in both late phase and delayed-type reactions, or inflammatory cell infiltration in the late phase reaction, but the inhibition was not significant. These results suggest that CyA eye drops are useful for suppressing ocular symptoms in both late phase and delayed-type reactions in allergic conjunctivitis models.
我们研究了环孢素 A(CyA)滴眼液对豚鼠过敏性结膜炎模型晚期和迟发型反应中眼部症状的疗效。卵清蛋白(OVA)和弗氏完全佐剂(FCA)的乳液被腹腔内注射到豚鼠中,并将 15%OVA 溶液局部应用于眼睛以引发晚期反应。在早期反应之后,在抗原挑战后 6 小时检测到充血、肿胀、水肿和分泌物评分增加,CyA 滴眼液显著抑制了水肿和分泌物评分增加、结膜组织中浸润性炎症细胞数量增加以及多形核白细胞中嗜酸性粒细胞的百分比增加。为了诱导迟发型反应,通过将 FCA 注射到足底来使豚鼠致敏,然后在 24 天后将纯化蛋白衍生物注射到睑结膜中。在迟发型过敏诱导后 6 小时检测到充血、肿胀和分泌物评分增加,CyA 滴眼液显著抑制了充血和肿胀评分的增加。相比之下,倍他米松磷酸钠滴眼液表现出抑制晚期和迟发型反应中症状或晚期反应中炎症细胞浸润的趋势,但抑制作用不显著。这些结果表明,CyA 滴眼液可有效抑制过敏性结膜炎模型中晚期和迟发型反应中的眼部症状。