Document Detail

Recombinant tumor necrosis factor increases pulmonary vascular permeability independent of neutrophils.
MedLine Citation:
PMID:  3143114     Owner:  NLM     Status:  MEDLINE    
We studied the effects of intravenous infusion of recombinant human tumor necrosis factor type alpha (rTNF-alpha; 12 micrograms/kg) on lung fluid balance in sheep prepared with chronic lung lymph fistulas. The role of neutrophils was examined in sheep made neutropenic with hydroxyurea (200 mg/kg for 4 or 5 days) before receiving rTNF-alpha. Infusion of rTNF-alpha resulted in respiratory distress and 3-fold increases in pulmonary arterial pressure and pulmonary vascular resistance within 15 min, indicating intense pulmonary vasoconstriction. Pulmonary lymph flow (i.e., net transvascular fluid filtration rate) and transvascular protein clearance rate (a measure of vascular permeability to protein) increased 2-fold within 30 min. The increased permeability was associated with leukopenia and neutropenia. The pulmonary hypertension and vasoconstriction subsided but fluid filtration and vascular permeability continued to increase. Sheep made neutropenic had similar increases in pulmonary transvascular fluid filtration and vascular permeability. rTNF-alpha also produced concentration-dependent increases in permeability of 125I-labeled albumin across ovine endothelial cell monolayers in the absence of neutrophils or other inflammatory mediators. The results indicate that rTNF-alpha increases pulmonary vascular permeability to protein by an effect on the endothelium.
C J Horvath; T J Ferro; G Jesmok; A B Malik
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  85     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1988 Dec 
Date Detail:
Created Date:  1988-12-30     Completed Date:  1988-12-30     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9219-23     Citation Subset:  IM    
Department of Physiology, Albany Medical College, Union University, NY 12208.
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MeSH Terms
Body Temperature / drug effects
Capillary Permeability / drug effects*
Carbon Dioxide / blood
Fibrin Fibrinogen Degradation Products / analysis
Fibrinogen / metabolism
Hydroxyurea / pharmacology
Leukocyte Count
Neutrophils / physiology*
Oxygen / blood
Pulmonary Circulation / drug effects*
Recombinant Proteins / pharmacology*
Reference Values
Tumor Necrosis Factor-alpha / pharmacology*
Grant Support
Reg. No./Substance:
0/Fibrin Fibrinogen Degradation Products; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 124-38-9/Carbon Dioxide; 127-07-1/Hydroxyurea; 7782-44-7/Oxygen; 9001-32-5/Fibrinogen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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