PMID- 8263817 OWN - NLM STAT- MEDLINE DCOM- 19940127 LR - 20131121 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 267 IP - 3 DP - 1993 Dec TI - Tumor necrosis factor-alpha mediates endotoxin-induced lung injury in platelet activating factor-primed rats. PG - 1550-7 AB - 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. FAU - Rabinovici, R AU - Rabinovici R AD - Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania. FAU - Bugelski, P J AU - Bugelski PJ FAU - Esser, K M AU - Esser KM FAU - Hillegass, L M AU - Hillegass LM FAU - Griswold, D E AU - Griswold DE FAU - Vernick, J AU - Vernick J FAU - Feuerstein, G AU - Feuerstein G LA - eng PT - Journal Article PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Antibodies, Monoclonal) RN - 0 (Lipopolysaccharides) RN - 0 (Platelet Activating Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 57576-52-0 (Thromboxane A2) RN - EC 1.11.1.7 (Peroxidase) RN - XXE1CET956 (Indomethacin) SB - IM MH - Animals MH - Antibodies, Monoclonal/pharmacology MH - Bronchoalveolar Lavage Fluid/cytology MH - Capillary Permeability/drug effects MH - Cricetinae MH - Indomethacin/pharmacology MH - Leukocyte Count MH - Leukocytes/cytology MH - *Lipopolysaccharides MH - Lung/anatomy & histology/blood supply/enzymology MH - Lung Diseases/*blood/*chemically induced/pathology MH - Male MH - Organ Size/drug effects MH - Peroxidase/metabolism MH - *Platelet Activating Factor MH - Rats MH - Rats, Sprague-Dawley MH - Thromboxane A2/biosynthesis/blood/*physiology MH - Time Factors MH - Tumor Necrosis Factor-alpha/immunology/metabolism/*physiology EDAT- 1993/12/01 00:00 MHDA- 1993/12/01 00:01 CRDT- 1993/12/01 00:00 PHST- 1993/12/01 00:00 [pubmed] PHST- 1993/12/01 00:01 [medline] PHST- 1993/12/01 00:00 [entrez] PST - ppublish SO - J Pharmacol Exp Ther. 1993 Dec;267(3):1550-7.