Isolated pulmonary infection acts as a source of systemic tumor necrosis factor.
OBJECTIVE
To investigate the local secretion of tumor necrosis factor (TNF) in the lung as a source for systemic TNF.


METHODS
Prospective, randomized experimental trials.


METHODS
Laboratory.


METHODS
Hartley guinea pigs.


METHODS
Female guinea pigs were challenged intratracheally with 10(3) to 10(9) Escherichia coli. Two and eight hrs after the bacterial challenge, colony-forming units of bacteria in the lung and blood, TNF and prostaglandin E2 (PGE2) in the bronchoalveolar lavage fluid, and serum TNF concentrations were determined. At the same time, alveolar macrophages were harvested and cultured in vitro, and TNF and PGE2 secretions were measured.


RESULTS
TNF and PGE2 concentrations were either not detected in bronchoalveolar lavage fluid or were found in very low levels in control animals. High concentrations of TNF and PGE2, however, were found in bacteria-challenged animals. Two hours after inoculation of bacteria, TNF in the bronchoalveolar lavage fluid had a significant correlation with TNF values in the serum. The TNF concentration in aortic blood was significantly higher than TNF concentration in right atrial blood. For comparable inocula, TNF in the bronchoalveolar lavage fluid after 8 hrs was significantly lower than at 2 hrs, but PGE2 levels remained high. Lipopolysaccharide-stimulated alveolar macrophage secretion of TNF in vitro was depressed in animals with high PGE2 levels in bronchoalveolar lavage fluid and high numbers of viable bacteria in the lungs.


CONCLUSIONS
During pulmonary Gram-negative infection, the lungs may be a major source of TNF in the blood. The magnitude of TNF secretion by the lungs is highly dependent on the intensity of infection during its early stages. By 8 hrs after onset of infection, TNF secretion appears to downregulate, possibly by endogenous PGE2.
Fukushima
R
R
Department of Surgery, University of Cincinnati School of Medicine, OH 45267-0558.
Alexander
J W
JW
Gianotti
L
L
Ogle
C K
CK
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004927:Escherichia coli Infections / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D008171:Lung Diseases / Q000378:metabolism* / Q000382:microbiology; D011446:Prospective Studies; D011458:Prostaglandins E / Q000737:chemistry / Q000378:metabolism; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism*
D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha