Pentoxifylline prevents tumor necrosis factor-induced lung injury.
Human tumor necrosis factor-alpha (TNF) is a monokine produced by mononuclear cells after many stimuli, including bacterial endotoxin. Full exploration of its antineoplastic effects has been limited by side effects. We have previously shown that the administration of TNF to guinea pigs is associated with a syndrome similar to gram-negative septic shock, which includes capillary permeability lung injury. In this study, we measured the effects of pentoxifylline (PTX) on parameters of TNF-induced lung injury including: lung wet-to-dry weight ratio, the ratio of lung-to-plasma 125I-labeled albumin (albumin index), bronchoalveolar lavage (BAL) and peripheral leukocyte counts, and serial measurements of mean arterial pressure (MAP). Four groups of animals were studied: a TNF group received 3.75 x 10(6) U/kg TNF; a PTX group received a 20-mg/kg bolus of PTX followed by an infusion of 6 mg/kg/h; the PTX-TNF group received both; and the final group was a saline control. ANOVA analysis revealed significant elevations of lung wet-to-dry ratio only in the TNF group (5.9 [5.6 to 6.3], p less than 0.001), expressed as the mean followed by 95% confidence intervals). Lung albumin index was elevated only in the TNF group (0.24 [0.19 to 0.29], p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lilly
C M
CM
Department of Medicine, Stanford University Medical Center, California 94305-5204.
Sandhu
J S
JS
Ishizaka
A
A
Harada
H
H
Yonemaru
M
M
Larrick
J W
JW
Shi
T X
TX
O'Hanley
P T
PT
Raffin
T A
TA
D000818:Animals; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006168:Guinea Pigs; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D009929:Organ Size; D010431:Pentoxifylline / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D013047:Specific Pathogen-Free Organisms; D013805:Theobromine / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000633:toxicity*
D014409:Tumor Necrosis Factor-alpha; D013805:Theobromine; D010431:Pentoxifylline