Tamura Tadafumi, Komai Masato
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Int Immunopharmacol. 2008 Jun;8(6):916-21. doi: 10.1016/j.intimp.2008.02.009. Epub 2008 Mar 18.
The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. In patients with AR, levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) increase. Olopatadine hydrochloride (olopatadine) is an anti-allergic agent with histamine H1 receptor antagonistic action. To investigate whether olopatadine has an effect on inflammatory reactions, toluene-2,4-diisocyanate (TDI)-sensitized rats were used as an animal model of nasal allergy. Nasal allergy signs (sneezing, rhinorrhea and inflammation) were induced after TDI challenge. Amounts of NGF and VEGF in the nasal lavage fluid increased. Olopatadine reduced nasal allergy signs and inhibited increases in NGF and VEGF. These findings suggest that the increases in NGF and VEGF production are involved in the mechanism responsible for nasal allergy signs in TDI-challenged rats. Other histamine H1 receptor antagonists did not inhibit and instillation of histamine did not increase TDI-induced NGF and VEGF production. Therefore, olopatadine appears to exert additional biological effects other than its blockade of the histamine H(1) receptor. These results suggest that suppression of neurogenic inflammatory reactions might be partially involved in the improvement of allergy signs after treatment with olopatadine.
变应性鼻炎(AR)的主要症状为打喷嚏、流涕和鼻塞。在AR患者中,神经生长因子(NGF)和血管内皮生长因子(VEGF)水平会升高。盐酸奥洛他定(奥洛他定)是一种具有组胺H1受体拮抗作用的抗过敏药物。为研究奥洛他定是否对炎症反应有影响,将甲苯-2,4-二异氰酸酯(TDI)致敏大鼠作为鼻过敏动物模型。在TDI激发后诱发鼻过敏体征(打喷嚏、流涕和炎症)。鼻灌洗液中NGF和VEGF的量增加。奥洛他定减轻了鼻过敏体征,并抑制了NGF和VEGF的增加。这些发现表明,NGF和VEGF产生的增加参与了TDI激发大鼠鼻过敏体征的机制。其他组胺H1受体拮抗剂没有抑制作用,组胺滴注也没有增加TDI诱导的NGF和VEGF产生。因此,奥洛他定似乎除了阻断组胺H(1)受体外,还发挥了其他生物学作用。这些结果表明,抑制神经源性炎症反应可能部分参与了奥洛他定治疗后过敏体征的改善。