Tumor necrosis factor-alpha mediates endotoxin-induced lung injury in platelet activating factor-primed rats.
We have reported recently that lipopolysaccharide endotoxin and platelet activating factor cooperate in priming relationships to elicit lung microvascular injury. Lung injury was associated with elevated serum levels of tumor necrosis factor-alpha (TNF alpha) and histological findings highly reminiscent of the adult respiratory distress syndrome. The present study was designed to examine the role of TNF alpha in lipopolysaccharide/platelet activating factor-induced lung injury by utilizing a highly specific monoclonal antibody which block TNF alpha actions (anti-TNF alpha monoclonal antibody). Pretreatment with anti-TNF alpha monoclonal antibody (2.5-25 mg/kg i.v., n = 5-9) dose-dependently prevented the lipopolysaccharide/platelet activating factor-induced histopathological changes, lung edema (P < .01), lung myeloperoxidase activity (P < .01), elevation of neutrophil count in bronchoalveolar lavage fluid (P < .01) and increased serum thromboxane B2 (P < .01). Indomethacin (6 mg/kg i.v., n = 5) failed to modify the lung injury despite complete inhibition of thromboxane B2 formation (P < .05). These data suggest that TNF alpha might play a key role in initiation of the early inflammatory changes which lead to adult respiratory distress syndrome.
Rabinovici
R
R
Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania.
Bugelski
P J
PJ
Esser
K M
KM
Hillegass
L M
LM
Griswold
D E
DE
Vernick
J
J
Feuerstein
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D006224:Cricetinae; D007213:Indomethacin / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology; D008070:Lipopolysaccharides; D008168:Lung / Q000033:anatomy & histology / Q000098:blood supply / Q000201:enzymology; D008171:Lung Diseases / Q000097:blood* / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D013928:Thromboxane A2; D009195:Peroxidase; D007213:Indomethacin