Buscaglia S, Paolieri F, Catrullo A, Fiorino N, Riccio A M, Pesce G, Montagna P, Bagnasco M, Ciprandi G, Canonica G W
Department of Internal Medicine, DIMI, University of Genoa, Italy.
Clin Exp Allergy. 1996 Oct;26(10):1188-96.
Levocabastine is a selective topical H1 antagonist, effective in the treatment of seasonal allergic rhinitis and conjunctivitis.
We evaluated the possible effects of levocabastine eye drops on early (EPR) and late phase (LPR) inflammatory changes induced by allergen-specific conjunctival challenge (ASCC). We focused our attention on the possible effect of levocabastine on expression of the intracellular adhesion molecule-1 (ICAM-1) on epithelial cells. Such a phenomenon is likely to play an important role in allergic inflammation.
The study was a double-blind, placebo-controlled, randomized trial, performed in cross-over, outside the pollen season. Ten out-patients suffering from allergic rhinoconjunctivitis due to parietaria judaica (wall parietary) were enrolled. Patients randomly received levocabastine eye drops (0.5 mg/mL) or placebo eyedrops, one drop in the left eye (right eye as control), 30 min before ASCC. Clinical evaluation (hyperaemia, burning-itching, lacrimation and eyelid swelling) and cytological assessment (number of neutrophils, eosinophils and lymphocytes, and ICAM-1 expression on conjunctival epithelium) were evaluated at baseline, 30 min and 6 h after ASCC. In parallel, we evaluated the in vitro effect of levocabastine at concentrations ranging from 2 x 10(-9) M to 2 x 10(-5) M on ICAM-1 expression and shedding by a continuously cultured differentiated epithelial cell line (WK).
Levocabastine reduced symptom scores during EPR (15 min and 30 min, P < 0.002), inflammatory cell infiltration during EPR (P < 0.002 for neutrophils, eosinophils and lymphocytes) and ICAM-1 expression on epithelium both during EPR (P < 0.002) and LPR (P < 0.02). LPR symptom scores and inflammatory cell infiltration were only slightly modified by levocabastine treatment. In vitro levocabastine at 2 x 10(-5) M concentration was able to down-regulate basal ICAM-1 expression, although it exerted no effect on ICAM-1 release by epithelium.
Levocabastine exerts anti-allergic activity, in that it reduces in vivo inflammatory cell infiltration due to ASCC, and also adhesion molecule expression on conjunctival epithelium. The latter phenomenon may be due, at least in part, to a direct effect of levocabastine on epithelial cells.
左卡巴斯汀是一种选择性局部用H1拮抗剂，对季节性变应性鼻炎和结膜炎有效。
我们评估了左卡巴斯汀滴眼液对变应原特异性结膜激发试验（ASCC）诱导的早期（EPR）和晚期（LPR）炎症变化的可能影响。我们重点关注左卡巴斯汀对上皮细胞细胞间黏附分子-1（ICAM-1）表达的可能影响。这种现象可能在变应性炎症中起重要作用。
本研究是一项双盲、安慰剂对照、随机试验，在花粉季节之外进行交叉试验。纳入10例因墙草引起变应性鼻结膜炎的门诊患者。患者在ASCC前30分钟随机接受左卡巴斯汀滴眼液（0.5mg/mL）或安慰剂滴眼液，左眼滴一滴（右眼作为对照）。在基线、ASCC后30分钟和6小时评估临床症状（充血、烧灼样瘙痒、流泪和眼睑肿胀）和细胞学指标（中性粒细胞、嗜酸性粒细胞和淋巴细胞数量以及结膜上皮细胞ICAM-1表达）。同时，我们评估了浓度范围为2×10⁻⁹M至2×10⁻⁵M的左卡巴斯汀对连续培养的分化上皮细胞系（WK）ICAM-1表达和脱落的体外影响。
左卡巴斯汀降低了EPR期间的症状评分（15分钟和30分钟，P<0.002）、EPR期间的炎症细胞浸润（中性粒细胞、嗜酸性粒细胞和淋巴细胞P<0.002）以及EPR期间（P<0.002）和LPR期间（P<0.02）上皮细胞上ICAM-1的表达。左卡巴斯汀治疗对LPR症状评分和炎症细胞浸润仅有轻微影响。体外实验中，2×10⁻⁵M浓度的左卡巴斯汀能够下调基础ICAM-1表达，尽管它对上皮细胞释放ICAM-1没有影响。
左卡巴斯汀具有抗过敏活性，因为它可减少ASCC引起的体内炎症细胞浸润，并降低结膜上皮细胞上黏附分子的表达。后一种现象可能至少部分归因于左卡巴斯汀对上皮细胞的直接作用。
