Sorkness R L, Castleman W L, Kumar A, Kaplan M R, Lemanske R F
Division of Allergy, Departments of Medicine and Pediatrics, and School of Pharmacy, University of Wisconsin, Madison, Wisconsin, USA.
Am J Respir Crit Care Med. 1999 Aug;160(2):705-10. doi: 10.1164/ajrccm.160.2.9810002.
After viral bronchiolitis at an early age, Brown Norway (BN) rats develop chronic airway dysfunction consisting of inflammation, remodeling, episodic reversible obstruction, and hyperresponsiveness. We hypothesized that supplementation of interferon gamma (IFN-gamma) during viral illness would alter the inflammatory response and attenuate the postviral sequelae. Weanling rats were treated daily with aerosolized interferon gamma (IFN-gamma), from 2 d prior through 7 d after inoculation, and compared with saline-treated infected rats and with noninfected control rats. The IFN-gamma treatment had no significant effect on viral titers, growth retardation, or total bronchoalveolar leukocytes, but there was a slight decrease in lung interleukin-4 (IL-4) mRNA (p = 0.015) during the first week. Despite having minimal effects on the acute illness, the IFN-gamma had marked effects on postviral sequelae, the IFN-gamma group having less bronchiolar inflammation (p = 0.025) and fibrosis (p = 0.01), and lacking abnormalities in pulmonary resistance (p = 0.028) and dynamic compliance (p = 0.006) compared with the untreated postviral group. We conclude that IFN-gamma modulated the inflammatory response to viral illness, such that acute airway injury did not evolve into chronic airway dysfunction. If similar processes contribute to the development of human asthma, it may be possible to interrupt the progression of airway dysfunction with an early immunomodulatory intervention.
幼年感染病毒性细支气管炎后，棕色挪威（BN）大鼠会出现慢性气道功能障碍，包括炎症、重塑、发作性可逆性阻塞和高反应性。我们假设在病毒感染期间补充干扰素γ（IFN-γ）会改变炎症反应并减轻病毒感染后的后遗症。从接种前2天到接种后7天，对断奶大鼠每日进行雾化干扰素γ（IFN-γ）治疗，并与盐水处理的感染大鼠和未感染的对照大鼠进行比较。IFN-γ治疗对病毒滴度、生长迟缓或支气管肺泡白细胞总数没有显著影响，但在第一周肺白细胞介素-4（IL-4）mRNA略有下降（p = 0.015）。尽管对急性疾病影响极小，但IFN-γ对病毒感染后的后遗症有显著影响，与未治疗的病毒感染后组相比，IFN-γ组的细支气管炎症（p = 0.025）和纤维化（p = 0.01）较轻，且肺阻力（p = 0.028）和动态顺应性（p = 0.006）无异常。我们得出结论，IFN-γ调节了对病毒感染的炎症反应，使急性气道损伤不会演变为慢性气道功能障碍。如果类似的过程导致人类哮喘的发生，那么通过早期免疫调节干预可能中断气道功能障碍的进展。
