Buijs J, Egbers M W, Lokhorst W H, Savelkoul H F, Nijkamp F P
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, The Netherlands.
Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):873-8. doi: 10.1164/ajrccm.151.3.7881685.
The immunoinflammatory response to parasitic nematode infections and allergic diseases have some similarities, the most profound being the increases in eosinophils and serum total IgE concentration. Whether parasitic infections stimulate or inhibit allergic asthma is a matter of debate. We investigated the effect of Toxocara canis (T. canis) infection on airway function in BALB/c mice at various days post-infection. Within 24 h after infection, the trachea responded hyperreactive to carbachol stimulation. Eosinophils, and to a lesser degree lymphocytes, infiltrated the airways causing interstitial and alveolar inflammation (7 d post-infection). Concurrently with cell infiltration, the trachea became hyporesponsive to carbachol whereas the pulmonary resistance was increased and the dynamic compliance decreased. The hyporeactive response could be simulated in vitro by incubating normal tracheae with eosinophil-enriched bronchoalveolar lavage cells obtained from infected mice. The response depended on the number of cells added to the medium, a lower number causing a hyper- and a higher number a hyporeactive response. Anti-interleukin-5 (anti-IL-5) producing hybridoma cells given simultaneously with T. canis infection inhibited eosinophil infiltration in the airways but not that of lymphocytes. Anti-IL-5 treatment prevented tracheal hyporeactivity but not perivascular and peribronchial edema, increased pulmonary resistance, or decreased dynamic compliance. Treatment with isotype control antibody did not affect eosinophil number nor the observed changes in airway functions. It was concluded that T. canis-induced airway inflammation coincided with increased pulmonary resistance, decreased dynamic compliance, and perivascular/peribronchial edema. These phenomena were independent on the presence of eosinophils, whereas tracheal hyporeactivity was clearly associated with airway eosinophilia.
对寄生线虫感染和过敏性疾病的免疫炎症反应有一些相似之处，最显著的是嗜酸性粒细胞增多和血清总IgE浓度升高。寄生虫感染是刺激还是抑制过敏性哮喘是一个有争议的问题。我们研究了犬弓首线虫（T. canis）感染对BALB/c小鼠感染后不同天数气道功能的影响。感染后24小时内，气管对卡巴胆碱刺激反应呈高反应性。嗜酸性粒细胞以及程度较轻的淋巴细胞浸润气道，导致间质和肺泡炎症（感染后7天）。与细胞浸润同时，气管对卡巴胆碱反应性降低，而肺阻力增加，动态顺应性降低。通过用从感染小鼠获得的富含嗜酸性粒细胞的支气管肺泡灌洗细胞孵育正常气管，可在体外模拟这种低反应性反应。该反应取决于添加到培养基中的细胞数量，细胞数量较少会导致高反应性，而细胞数量较多则会导致低反应性。与犬弓首线虫感染同时给予产生抗白细胞介素-5（抗IL-5）的杂交瘤细胞可抑制气道中嗜酸性粒细胞的浸润，但不能抑制淋巴细胞的浸润。抗IL-5治疗可预防气管低反应性，但不能预防血管周围和支气管周围水肿、肺阻力增加或动态顺应性降低。用同型对照抗体治疗不影响嗜酸性粒细胞数量，也不影响观察到的气道功能变化。得出的结论是，犬弓首线虫诱导的气道炎症与肺阻力增加、动态顺应性降低以及血管周围/支气管周围水肿同时出现。这些现象与嗜酸性粒细胞的存在无关，而气管低反应性显然与气道嗜酸性粒细胞增多有关。
