McKinney W J, Jaskot R H, Richards J H, Costa D L, Dreher K L
Center for Environmental Medicine, University of North Carolina, Chapel Hill, USA.
Am J Respir Cell Mol Biol. 1998 May;18(5):696-705. doi: 10.1165/ajrcmb.18.5.2928.
Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.
先前的研究表明，让动物单次暴露于臭氧（O₃）环境中，可诱导其对随后的O₃攻击产生的急性损伤效应产生保护作用或适应性反应。尽管已经提出了多种机制来解释这种反应，但似乎都不能完全解释清楚。我们研究了白细胞介素（IL）-6在诱导对O₃所致肺损伤的适应性反应中可能发挥的作用。与白天暴露相比，夜间暴露于0.5 ppm O₃的大鼠支气管肺泡灌洗液中IL-6水平在统计学上显著增加了29倍，尽管每次暴露诱导的炎症动力学相似。与最初白天暴露的动物相比，最初夜间暴露于O₃的动物在随后再次暴露于O₃时炎症程度较轻。气管内和腹腔内预先给予IL-6，随后暴露于O₃的大鼠与各自的对照组相比，细胞炎症程度较轻。在夜间O₃暴露前用抗IL-6受体抗体（ra）预处理大鼠，完全消除了O₃诱导的细胞适应性反应，而不影响最初夜间O₃暴露诱导的炎症反应。事实上，给予抗IL-6ra会增加第二次O₃暴露后的中性粒细胞流入。抗IL-6ra治疗并未改变肺水肿适应性反应，这表明O₃诱导的细胞和水肿适应性反应是由不同机制调节的。我们的数据表明，肺抗氧化剂的动员在IL-6介导的早期细胞适应性反应中不起作用，并提示IL-6是O₃诱导的细胞适应性反应的重要介质。
