Gudewicz P W, Ferguson J L, Kapin M A, Jaffe R C
Adv Shock Res. 1981;5:123-32.
Thermal injury often results in the development of compromised host defense mechanisms against infections (eg, increased incidence of pulmonary sepsis in postburn animals has been attributed to impaired cellular defenses in the lung). Recent reports have demonstrated that high dose glucocorticoid therapy used in the treatment of inflammatory diseases and shock also results in an increased susceptibility of the host to pulmonary sepsis. Although several defense mechanisms are available to the respiratory tract combating bacterial challenges, the major cellular defense is the alveolar macrophage, which phagocytizes infectious agents and potentially toxic particulate matter that infiltrate the lower respiratory tract. Recent evidence has demonstrated that high doses of cortisol in vivo impair both functional and metabolic activities of the alveolar macrophage. However, there is little information regarding whether alterations in endogenous levels of glucocorticoids following systemic injury can mediate similar defects on the cellular defenses of the lung. The present study demonstrated that both high dose glucocorticoid treatment and burn injury severely impaired the functional activity of the resident lung macrophage. The phagocytic cell population in the lower respiratory tract was reduced by more than 50%, 24 hr following either burn injury or a 7 day cortisone regimen. Furthermore, the remaining alveolar macrophages lavaged from either experimental group demonstrated a marked impairment in phagocytic activity. The combination of a reduced macrophage population in the lung and a decreased phagocytic activity of the residual cells indicated a severe deficiency in the total lung phagocytic capacity. The 7 day cortisone treatment markedly elevated plasma (greater than 400%) and lung lavage (greater than 200%) levels of cortisol. Although plasma levels of cortisol were also significantly increased (greater than 50%) 24 hr post burn injury, lung lavage cortisol levels were not higher than saline-treated sham burn control values. However, lung lavage concentration of cortisol was increased over threefold following cortisone treatment and burn injury.
热损伤常导致宿主抗感染防御机制受损（例如，烧伤后动物肺部脓毒症发病率增加被归因于肺部细胞防御功能受损）。最近的报告表明，用于治疗炎症性疾病和休克的高剂量糖皮质激素疗法也会导致宿主对肺部脓毒症的易感性增加。尽管呼吸道有多种防御机制来应对细菌挑战，但主要的细胞防御是肺泡巨噬细胞，它吞噬侵入下呼吸道的感染因子和潜在有毒颗粒物。最近的证据表明，体内高剂量的皮质醇会损害肺泡巨噬细胞的功能和代谢活动。然而，关于全身损伤后内源性糖皮质激素水平的改变是否会对肺部细胞防御产生类似的缺陷，目前知之甚少。本研究表明，高剂量糖皮质激素治疗和烧伤均严重损害了肺内常驻巨噬细胞的功能活性。烧伤或可的松治疗7天后24小时，下呼吸道吞噬细胞数量减少了50%以上。此外，从任一实验组灌洗出的剩余肺泡巨噬细胞吞噬活性均显著受损。肺内巨噬细胞数量减少与残余细胞吞噬活性降低相结合，表明肺总吞噬能力严重不足。可的松治疗7天显著提高了血浆（超过400%）和肺灌洗（超过200%）中的皮质醇水平。虽然烧伤后24小时血浆皮质醇水平也显著升高（超过50%），但肺灌洗皮质醇水平不高于生理盐水处理的假烧伤对照值。然而，可的松治疗和烧伤后肺灌洗皮质醇浓度增加了三倍多。
