The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure
| Autor: | Peter Q. Eichacker, W. D. Hoffman, L. C. Cork, Charles Natanson, Zenaide M.N. Quezado, C A Koev, Ronald J. Elin, I. Yatsiv, J. A. Winkelstein |
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| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Multiple Organ Failure Immunology Hemodynamics Biology Kidney Dogs Internal medicine Infusion Procedure Escherichia coli medicine Animals Immunology and Allergy Prospective Studies Pulmonary wedge pressure Lung Analysis of Variance medicine.diagnostic_test Tumor Necrosis Factor-alpha Heart Complement C3 Articles Hydrogen-Ion Concentration medicine.disease Shock Septic Complement system Endotoxins Bronchoalveolar lavage Endocrinology Liver Shock (circulatory) Female Tumor necrosis factor alpha medicine.symptom Multiple organ dysfunction syndrome Bronchoalveolar Lavage Fluid |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.179.2.569 |
| Popis: | We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock. |
| Databáze: | OpenAIRE |
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