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Lung cytokine production was examined after the intravenous administration of endotoxin to 23 normal human subjects. Bronchoalveolar lavage (BAL) was performed 7 days before and 1.5 or 5 h after endotoxin (4 ng/kg). Cytokine mRNA was evaluated in cell pellets (> 98% macrophages) by use of reverse transcription and the polymerase chain reaction. Immunoreactivity was measured by enzyme-linked immunosorbent assay of 20- to 40-fold concentrated BAL. Interleukin- (IL) 8 was detected in BAL (4-130 pg/ml) but not in the serum at baseline. Few neutrophils were found in BAL (< 1%) despite this IL-8 gradient. Peak serum IL-8 levels occurred 2 h after endotoxin (3,930 +/- 241 pg/ml), but BAL neutrophils and IL-8 did not increase. Peak serum tumor necrosis factor (TNF) levels occurred 1.5 h after endotoxin (1,844 +/- 210 pg/ml), but TNF was detected in only 1 of 20 BAL samples. TNF and IL-8 mRNA were detected by polymerase chain reaction in > 70% of the BAL samples before endotoxin, whereas IL-1 alpha, IL-1 beta, and IL-6 were detected in < 25% of the BAL samples. After endotoxin, no change was detected in cytokine mRNA expression. Actinomycin D treatment of the BAL did not alter the pattern of cytokine mRNA expression. These data suggest that mechanisms exist to insulate the alveolar space from the stimulatory effects of endotoxin and high circulating levels of cytokines. Additional factors appear to control the chemotactic effects of IL-8 on neutrophils in the air spaces during acute systemic inflammation.

A closed-book, multiple-choice examination following this article tests your under standing of the following objectives:1. Describe the medical indications for the use of extracorporeal membrane oxygenation (ECMO ACNP-BCBackground Extracorporeal membrane oxygenation (ECMO) is used for critically ill patients when conventional treatments for cardiac or respiratory failure are unsuccessful. Objectives To describe patient and treatment characteristics and discharge outcome for ECMO patients, determine which characteristics are associated with good (survival) versus poor (death before hospital discharge) outcomes, and compare characteristics of patients with cardiac versus respiratory failure indicating ECMO. Methods Single-center, retrospective review of all adult patients treated with ECMO from 2005 through 2009. Results A total of 212 patients received ECMO for cardiac (n = 126) or respiratory (n = 86) failure. Mean age was 51 (SD, 14.5) years; support duration was 135 (SD, 149) hours. Survival to discharge was 33% overall; 50% for respiratory indication and 21% for cardiac indication patients. Patients with poor outcomes were older (53 vs 47 years, P = .007), more likely to require cardiovascular support before ECMO (99% vs 91%; P = .02), and had more transfusions (48 vs 24 units, P = .005) and complications (99% vs 87%; P < .001) than did patients with good outcomes. For cardiac patients, older age was associated with poor outcome (poor, 55 vs good, 48 years; P = .01). For respiratory patients, poor outcome was associated with more ventilator days before ECMO (poor, 6 vs good, 3; P = .01), higher peak inspiratory pressure (poor, 39 vs good, 35 cm H 2 O; P = .02), and lower pulmonary compliance (poor, 19 vs good, 25 mL/cm H 2 O; P = .008). Conclusions Patients with respiratory indications for ECMO experienced better survival than did cardiac patients. Increasing age was associated with poor outcome. Complications, regardless of ECMO indication, were common and associated with poor outcome.