Sanico A M, Atsuta S, Proud D, Togias A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
J Allergy Clin Immunol. 1997 Nov;100(5):632-41. doi: 10.1016/s0091-6749(97)70167-2.
Nerve involvement has been implicated in the pathophysiology of chronic respiratory inflammatory diseases. Peptidergic nerve stimulation has been shown to induce leukocyte activation and plasma extravasation in the airways of various animal species. The occurrence of this phenomenon of neurogenic inflammation in the human airway, however, has not been established.
We conducted this study to determine whether neuronal stimulation can induce reproducible and dose-dependent inflammatory changes in the human upper airway.
Ten volunteers with active allergic rhinitis participated in the study. Capsaicin, the pungent component of hot pepper that specifically stimulates afferent nerve fibers, was administered by means of nasal spray in doses of 1 microg, 10 microg, and 100 microg in a double-blind, randomized, crossover manner with 1 week between doses. Symptom scores before and after capsaicin nasal challenge were recorded by using visual analog scales. Nasal lavage fluids collected before and at 30 minutes, 1 hour, and 4 hours after capsaicin challenge were analyzed for leukocyte counts; albumin and lysozyme levels were measured to evaluate effects on plasma leakage and gland secretion, respectively.
Capsaicin nasal challenge produced symptoms of burning, congestion, and rhinorrhea. Leukocyte counts or albumin and lysozyme levels were not significantly increased after administration of 1 microg of capsaicin at any time point. On the other hand, there were significant increases in leukocyte counts 1 hour (p < 0.05) and 4 hours (p = 0.008) after 10 microg of capsaicin and 30 minutes (p = 0.009), 1 hour (p = 0.007), and 4 hours (p = 0.007) after 100 microg of capsaicin. Albumin and lysozyme levels were both significantly increased 30 minutes after 10 microg and 100 microg of capsaicin (p = 0.005 for both). Comparison of changes in symptom scores, leukocyte counts, and albumin and lysozyme levels among the three capsaicin challenges indicated generally increasing effects with higher capsaicin doses.
Capsaicin-sensitive nerve stimulation in subjects with active allergic rhinitis produces reproducible and dose-dependent leukocyte influx, albumin leakage, and glandular secretion. These results provide in vivo evidence for the occurrence of neurogenic inflammation in the human upper airway with active allergic disease.
神经受累已被认为与慢性呼吸道炎症性疾病的病理生理学有关。在多种动物物种的气道中，肽能神经刺激已被证明可诱导白细胞活化和血浆渗出。然而，这种神经源性炎症现象在人类气道中的发生尚未得到证实。
我们进行这项研究以确定神经元刺激是否能在人类上呼吸道中诱导可重复的、剂量依赖性的炎症变化。
10名患有活动性变应性鼻炎的志愿者参与了该研究。辣椒素是辣椒中的辛辣成分，可特异性刺激传入神经纤维，通过鼻腔喷雾以1微克、10微克和100微克的剂量双盲、随机、交叉给药，给药间隔为1周。使用视觉模拟量表记录辣椒素鼻腔激发前后的症状评分。分析辣椒素激发前及激发后30分钟、1小时和4小时收集的鼻腔灌洗液中的白细胞计数；分别测量白蛋白和溶菌酶水平以评估对血浆渗漏和腺体分泌的影响。
辣椒素鼻腔激发产生了烧灼感、充血和流涕等症状。在任何时间点，给予1微克辣椒素后白细胞计数、白蛋白和溶菌酶水平均未显著增加。另一方面，给予10微克辣椒素后1小时（p<0.05）和4小时（p = 0.008）以及给予100微克辣椒素后30分钟（p = 0.009）、1小时（p = 0.007）和4小时（p = 0.007）白细胞计数显著增加。给予10微克和100微克辣椒素后30分钟白蛋白和溶菌酶水平均显著增加（两者p = 0.005）。三种辣椒素激发之间症状评分、白细胞计数以及白蛋白和溶菌酶水平变化的比较表明，辣椒素剂量越高，作用通常越强。
对患有活动性变应性鼻炎的受试者进行辣椒素敏感神经刺激会产生可重复的、剂量依赖性的白细胞流入、白蛋白渗漏和腺体分泌。这些结果为患有活动性变应性疾病的人类上呼吸道中神经源性炎症的发生提供了体内证据。
