Nelson S, Summer W, Bagby G, Nakamura C, Stewart L, Lipscomb G, Andresen J
Department of Pulmonary Medicine, Louisiana State University Medical Center, New Orleans 70112.
J Infect Dis. 1991 Nov;164(5):901-6. doi: 10.1093/infdis/164.5.901.
Ethanol suppresses functions of the polymorphonuclear leukocyte (PMNL), seriously compromising normal host defenses against pneumonia. Because granulocyte colony-stimulating factor (G-CSF) augments the number and function of PMNL, the effect of G-CSF on the antibacterial defenses of the lung in normal and acutely intoxicated rats was studied. Animals received G-CSF or vehicle twice a day for 2 days, then ethanol or saline, followed by challenge with Klebsiella pneumoniae. K. pneumoniae elicited an intrapulmonary influx of PMNL in control rats that was markedly suppressed by prior ethanol administration. G-CSF augmented the recruitment of PMNL into the lungs of control rats and significantly attenuated the adverse effects of ethanol on PMNL entry into the lung. G-CSF enhanced intrapulmonary bactericidal activity against this pathogen in normal and ethanol-treated rats. All intoxicated rats pretreated with the vehicle died, while greater than 90% of rats pretreated with G-CSF survived. These findings suggest a potential role for G-CSF in mitigating the adverse effects of ethanol on PMNL delivery and pulmonary host defenses.
乙醇会抑制多形核白细胞(PMNL)的功能,严重损害宿主对肺炎的正常防御能力。由于粒细胞集落刺激因子(G-CSF)可增加PMNL的数量和功能,因此研究了G-CSF对正常和急性中毒大鼠肺部抗菌防御的影响。动物每天接受两次G-CSF或赋形剂,持续2天,然后给予乙醇或生理盐水,随后用肺炎克雷伯菌进行攻击。肺炎克雷伯菌在对照大鼠中引起肺内PMNL流入,而预先给予乙醇可明显抑制这种流入。G-CSF增加了对照大鼠肺部PMNL的募集,并显著减轻了乙醇对PMNL进入肺部的不利影响。G-CSF增强了正常和乙醇处理大鼠肺部对该病原体的杀菌活性。所有用赋形剂预处理的中毒大鼠均死亡,而用G-CSF预处理的大鼠存活率超过90%。这些发现表明,G-CSF在减轻乙醇对PMNL递送和肺部宿主防御的不利影响方面具有潜在作用。