Lack G, Bradley K L, Hamelmann E, Renz H, Loader J, Leung D Y, Larsen G, Gelfand E W
Department of Pediatrics, National Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
J Immunol. 1996 Aug 15;157(4):1432-9.
The effects of nebulized IFN-gamma on primary and secondary IgE production and development of airway hyper-responsiveness (AHR) were investigated. BALB/c mice received primary exposure to aerosolized OVA daily for 10 days and developed anti-OVA IgE responses, immediate cutaneous reactivity to OVA, and altered airway function when assayed on day 12. After secondary exposure to OVA challenges on days 30 and 31, these mice developed an amplified IgE response, heightened cutaneous reactivity to OVA and AHR when measured on day 37. Administration of IFN-gamma for 13 days, beginning 3 days prior to and during primary OVA sensitization, resulted in a decrease in anti-OVA IgE, increases in serum anti-OVA IgG2a levels, a decrease in cutaneous reactivity to OVA, and normal airway function when assessed on day 12 after primary sensitization. This treatment also prevented the development of secondary anti-OVA IgE responses and altered airway responsiveness but did not induce a secondary rise in anti-OVA IgG2a in the serum measured on day 37. Treatment with IFN-gamma on days 26 to 30, well after primary responses were established but just prior to secondary OVA challenge, abolished the development of secondary anti-OVA IgE responses, resulted in an increase in anti-OVA IgG2a in the serum, and prevented the development of AHR. In vitro, CD4+ T cells obtained from OVA-sensitized mice treated with either "early" or "late" IFN-gamma inhibited IgE production. Delivery of IFN-gamma to the airways can prevent secondary allergen sensitization even after primary sensitization has been achieved and this effect is mediated by CD4+ T cells.
研究了雾化干扰素-γ对原发性和继发性IgE产生以及气道高反应性（AHR）发展的影响。BALB/c小鼠每天接受雾化卵清蛋白（OVA）的初次暴露，持续10天，并在第12天检测时产生了抗OVA IgE反应、对OVA的即刻皮肤反应性以及气道功能改变。在第30天和第31天再次暴露于OVA激发后，这些小鼠在第37天检测时出现了放大的IgE反应、对OVA的皮肤反应性增强和AHR。在初次OVA致敏前3天及致敏期间开始给予干扰素-γ 13天，导致抗OVA IgE减少，血清抗OVA IgG2a水平升高，对OVA的皮肤反应性降低，并且在初次致敏后第12天评估时气道功能正常。这种治疗还预防了继发性抗OVA IgE反应的发展并改变了气道反应性，但在第37天检测的血清中未诱导抗OVA IgG2a的二次升高。在初次反应建立后很久但在二次OVA激发前，于第26至30天用干扰素-γ治疗，消除了继发性抗OVA IgE反应的发展，导致血清中抗OVA IgG2a增加，并预防了AHR的发展。在体外，从用“早期”或“晚期”干扰素-γ治疗的OVA致敏小鼠获得的CD4+ T细胞抑制了IgE的产生。即使在已实现初次致敏后，将干扰素-γ递送至气道也可预防继发性过敏原致敏，并且这种作用由CD4+ T细胞介导。
