Abstract |
Bacterial lipopolysaccharide given intravenously at 30 mg/kg to anesthetized rats results in rapid systemic hypotension and hypovolemia, elaboration of cytokines, increased proteolysis and vascular endothelial dysfunction. When a monoclonal antibody SdJ5-1.17.15 (SdJ5) directed against the lipid A moiety of lipopolysaccharide was administered at (1.25 or 5.0 mg/kg) 5 min prior to the endotoxin, significant protection was afforded to rats. This protection was manifested by a significant reduction in the early hypotension, as well as attenuation of hypovolemia and proteolysis. To evaluate endothelial function, superior mesenteric artery rings were isolated from endotoxemic rats 4 h after endotoxic challenge. Lipopolysaccharide (LPS) significantly reduced superior mesenteric artery vasorelaxation to acetylcholine and A23187, two endothelium-dependent vasodilators, but not to NaNO2, an endothelium-independent vasodilator. SdJ5 significantly preserved vasorelaxation responses to both acetylcholine and A23187, indicating a marked degree of endothelial preservation by this anti- lipid A monoclonal antibody. The protection was dose-dependent since 0.3 mg/kg of SdJ5 did not provide significant protection in any variable measured. Moreover, there was no significant difference between the 1.25 mg/kg and 5.0 mg/kg dose of SdJ5. Furthermore, plasma concentrations of TNF-alpha, a cytokine involved in mediating many of the effects associated with endotoxemia, was significantly reduced in SdJ5-treated animals. Thus, SdJ5 appears to be capable of counteracting many of the in vivo sequelae of endotoxemia in rats.
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Authors | P S Mead, J P Guo, A M Lefer, S Pierce, M Palladino |
Journal | Methods and findings in experimental and clinical pharmacology
(Methods Find Exp Clin Pharmacol)
1994 Jul-Aug
Vol. 16
Issue 6
Pg. 405-12
ISSN: 0379-0355 [Print] Spain |
PMID | 7837831
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Blood Proteins
- Immunoglobulin M
- Lipid A
- Tumor Necrosis Factor-alpha
- Calcimycin
- Sodium Nitrite
- Acetylcholine
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Topics |
- Acetylcholine
(pharmacology)
- Analysis of Variance
- Animals
- Antibodies, Monoclonal
(administration & dosage, pharmacology, therapeutic use)
- Blood Proteins
(metabolism)
- Calcimycin
(pharmacology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Endothelium, Vascular
(drug effects)
- Humans
- Hypotension
(drug therapy)
- Immunoglobulin M
(immunology)
- Lipid A
(administration & dosage, immunology, toxicity)
- Male
- Mesenteric Arteries
(drug effects)
- Muscle Relaxation
(drug effects)
- Muscle, Smooth, Vascular
(drug effects)
- Rats
- Rats, Sprague-Dawley
- Shock, Septic
(drug therapy, metabolism, prevention & control)
- Sodium Nitrite
(pharmacology)
- Tumor Necrosis Factor-alpha
(metabolism)
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