Tumor necrosis factor causes increased pulmonary permeability and edema. Comparison to septic acute lung injury.
Tumor necrosis factor alpha (TNF), a monokine produced by mononuclear cells in response to bacterial endotoxin (LPS), creates a syndrome similar to septic shock in animal models. To study whether TNF could induce acute lung injury similar to that seen in gram-negative sepsis, we injected recombinant human TNF (rHuTNF alpha) into guinea pigs and monitored arterial blood gases, leukocyte counts, and left atrial (Pla), pulmonary artery (Ppa), and mean arterial pressures (MAP) serially for 8 h. Pulmonary histopathology was assessed microscopically, and cell counts and 125I-labeled albumin (125I-albumin) in bronchoalveolar lavage (BAL) fluid and lung wet/dry weight ratios were determined. Five groups of animals were studied; the 2 TNF groups received high (1.4 X 10(6) U/kg) or low (1.0 X 10(6) U/kg) doses of rHuTNF alpha, the sepsis group received 2 X 10(9) Escherichia coli/kg intravenously, and the control group received saline. An LPS control group receiving 40 ng/kg E. coli LPS was also included because the rHuTNF alpha contained a small amount of LPS as a contaminant. Pulmonary permeability was assessed by studying the Pla and the BAL fluid/plasma 125I-albumin ratio (permeability index). The permeability index was significantly increased in the high-dose TNF (0.0408 +/- 0.0041, p less than 0.05) and sepsis groups (0.0466 +/- 0.0068, p less than 0.01) relative to controls (0.0215 +/- 0.0028). The wet/dry lung weight ratios were also significantly increased in the high-dose TNF (6.07 +/- 0.29, p less than 0.05) and sepsis groups (6.22 +/- 0.30, p less than 0.05) relative to the control group (5.18 +/- 0.20).(ABSTRACT TRUNCATED AT 250 WORDS)
Stephens
K E
KE
Department of Medicine, Stanford University Medical Center, California 94305-5204.
Ishizaka
A
A
Larrick
J W
JW
Raffin
T A
TA
D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D004927:Escherichia coli Infections / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology; D010539:Permeability; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology; D018805:Sepsis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha