Wagenmann M, Baroody F M, Kagey-Sobotka A, Lichtenstein L M, Naclerio R M
Johns Hopkins University School of Medicine, Department of Medicine (Division of Clinical Immunology), Baltimore, Maryland.
J Allergy Clin Immunol. 1994 Mar;93(3):594-605. doi: 10.1016/s0091-6749(94)70071-0.
To investigate the role of H1 receptor-mediated effects in allergic rhinitis, we challenged 12 allergic volunteers with allergen 2 hours after administration of either placebo or 60 mg of terfenadine. Filter paper discs were used for the unilateral administration of allergen and the collection of nasal secretions. Secretion weights, levels of histamine in recovered nasal secretions, and nasal airway resistance (NAR) were measured for each nostril separately, and the number of sneezes was counted. After placebo treatment, allergen challenge led to significant increases in ipsilateral and contralateral secretion weights, ipsilateral histamine levels, ipsilateral NAR, and sneezing. Contralateral histamine levels were not elevated. H1 antagonism with terfenadine markedly reduced the number of sneezes and partially decreased ipsilateral and contralateral secretion weights, without affecting the increase in NAR. Terfenadine premedication also lowered the amount of histamine in ipsilateral secretions after allergen challenge. Performing identical nasal challenges with a 10-fold lower dose of antigen produced similar results. Previous studies showed that terfenadine had no effect on methacholine provocation and completely abolished ipsilateral and contralateral secretion weights after histamine challenge. We conclude that sneezing after allergen challenge is caused almost exclusively by a reflex initiated through H1 receptors and that H1 antagonism has no influence on allergen-induced increases in NAR. Unilateral allergen challenge leads to bilateral increases in secretion weights, which are only partially inhibited by terfenadine, suggesting the involvement of mediators other than histamine in the nasonasal reflex. As reported earlier, terfenadine also decreases allergen-induced histamine release after challenge with the highest dose of antigen.
为研究H1受体介导的效应在变应性鼻炎中的作用，我们在给予安慰剂或60mg特非那定2小时后，用变应原激发12名变应性志愿者。使用滤纸圆盘进行变应原的单侧给药及鼻分泌物的收集。分别测量每个鼻孔的分泌物重量、回收鼻分泌物中的组胺水平及鼻气道阻力（NAR），并计数喷嚏次数。安慰剂治疗后，变应原激发导致同侧和对侧分泌物重量、同侧组胺水平、同侧NAR及喷嚏次数显著增加。对侧组胺水平未升高。特非那定的H1拮抗作用显著减少了喷嚏次数，并部分降低了同侧和对侧分泌物重量，但未影响NAR的增加。特非那定预处理还降低了变应原激发后同侧分泌物中的组胺量。用10倍低剂量的抗原进行相同的鼻腔激发产生了相似的结果。先前的研究表明，特非那定对乙酰甲胆碱激发无影响，且在组胺激发后完全消除了同侧和对侧分泌物重量。我们得出结论，变应原激发后的喷嚏几乎完全由通过H1受体引发的反射引起，且H1拮抗作用对变应原诱导的NAR增加无影响。单侧变应原激发导致双侧分泌物重量增加，特非那定仅部分抑制该增加，提示除组胺外的其他介质参与了鼻鼻反射。如先前报道，特非那定在用最高剂量抗原激发后也可减少变应原诱导的组胺释放。
