In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.
This article has been cited by other articles:
Chen, W. H., Tae Jin Kang, , Bhattacharjee, A. K., Cross, A. S.
(2008). Intranasal administration of a detoxified endotoxin vaccine protects mice against heterologous Gram-negative bacterial pneumonia. Innate Immunity
14: 269-278
[Abstract]
McDonald, B., McAvoy, E. F., Lam, F., Gill, V., de la Motte, C., Savani, R. C., Kubes, P.
(2008). Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. JEM
205: 915-927
[Abstract][Full Text]
Cross, A. S., Chen, W. H., Levine, M. M.
(2008). A case for immunization against nosocomial infections. J. Leukoc. Biol.
83: 483-488
[Abstract][Full Text]
Marshall, J. C.
(2008). Sepsis: rethinking the approach to clinical research. J. Leukoc. Biol.
83: 471-482
[Abstract][Full Text]
Adams Waldorf, K. M., Persing, D., Novy, M. J., Sadowsky, D. W., Gravett, M. G.
(2008). Pretreatment With Toll-like Receptor 4 Antagonist Inhibits Lipopolysaccharide-Induced Preterm Uterine Contractility, Cytokines, and Prostaglandins in Rhesus Monkeys. Reproductive Sciences
15: 121-127
[Abstract]
Osuchowski, M. F., Welch, K., Siddiqui, J., Remick, D. G.
(2006). Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality. J. Immunol.
177: 1967-1974
[Abstract][Full Text]
Kaniuk, N. A., Vinogradov, E., Li, J., Monteiro, M. A., Whitfield, C.
(2004). Chromosomal and Plasmid-encoded Enzymes Are Required for Assembly of the R3-type Core Oligosaccharide in the Lipopolysaccharide of Escherichia coli O157:H7. J. Biol. Chem.
279: 31237-31250
[Abstract][Full Text]
Van Amersfoort, E. S., Van Berkel, T. J. C., Kuiper, J.
(2003). Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock. Clin. Microbiol. Rev.
16: 379-414
[Abstract][Full Text]
Bannerman, D. D., Goldblum, S. E.
(2003). Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis. Am. J. Physiol. Lung Cell. Mol. Physiol.
284: L899-L914
[Abstract][Full Text]
Yamamoto, H., Koizumi, T., Kaneki, T., Fujimoto, K., Kubo, K., Honda, T.
(2002). Direct hemoperfusion with polymyxin B-immobilized fiber improves shock and hypoxemia during endotoxemia in anesthetized sheep. Innate Immunity
8: 419-426
[Abstract]
Erwert, R. D., Winn, R. K., Harlan, J. M., Bannerman, D. D.
(2002). Shiga-like Toxin Inhibition of FLICE-like Inhibitory Protein Expression Sensitizes Endothelial Cells to Bacterial Lipopolysaccharide-induced Apoptosis. J. Biol. Chem.
277: 40567-40574
[Abstract][Full Text]
Hellman, J., Roberts, J. D. Jr., Tehan, M. M., Allaire, J. E., Warren, H. S.
(2002). Bacterial Peptidoglycan-associated Lipoprotein Is Released into the Bloodstream in Gram-negative Sepsis and Causes Inflammation and Death in Mice. J. Biol. Chem.
277: 14274-14280
[Abstract][Full Text]
Bannerman, D. D., Tupper, J. C., Erwert, R. D., Winn, R. K., Harlan, J. M.
(2002). Divergence of Bacterial Lipopolysaccharide Pro-apoptotic Signaling Downstream of IRAK-1. J. Biol. Chem.
277: 8048-8053
[Abstract][Full Text]
Schwartz, D. A.
(2002). The Genetics of Innate Immunity. Chest
121: 62S-68S
[Abstract][Full Text]
Hellman, J., Shaw Warren, H.
(2001). Outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein lipoprotein (MLP) are released in experimental Gram-negative sepsis. Innate Immunity
7: 69-72
[Abstract]
Dubois, M.-J., Vincent, J.-L.
(2000). Clinically-oriented therapies in sepsis: a review. Innate Immunity
6: 463-469
[Abstract]
Bennett-Guerrero, E., McIntosh, T. J., Barclay, G. R., Snyder, D. S., Gibbs, R. J., Mythen, M. G., Poxton, I. R.
(2000). Preparation and Preclinical Evaluation of a Novel Liposomal Complete-Core Lipopolysaccharide Vaccine. Infect. Immun.
68: 6202-6208
[Abstract][Full Text]
Keller, M. A., Stiehm, E. R.
(2000). Passive Immunity in Prevention and Treatment of Infectious Diseases. Clin. Microbiol. Rev.
13: 602-614
[Abstract][Full Text]
David, S. A., Awasthi, S. K., Balaram, P.
(2000). The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides. Innate Immunity
6: 249-256
[Abstract]
Hellman, J., Loiselle, P. M., Tehan, M. M., Allaire, J. E., Boyle, L. A., Kurnick, J. T., Andrews, D. M., Sik Kim, K., Warren, H. S.
(2000). Outer Membrane Protein A, Peptidoglycan-Associated Lipoprotein, and Murein Lipoprotein Are Released by Escherichia coli Bacteria into Serum. Infect. Immun.
68: 2566-2572
[Abstract][Full Text]
Hellman, J., Warren, H. S.
(1999). Antibodies against bacterial membrane proteins. Innate Immunity
5: 213-215
[Abstract]
David, S. A., Silverstein, R., Amura, C. R., Kielian, T., Morrison, D. C.
(1999). Lipopolyamines: Novel Antiendotoxin Compounds That Reduce Mortality in Experimental Sepsis Caused by Gram-Negative Bacteria. Antimicrob. Agents Chemother.
43: 912-919
[Abstract][Full Text]
Nnalue, N. A.
(1999). All Accessible Epitopes in the Salmonella Lipopolysaccharide Core Are Associated with Branch Residues. Infect. Immun.
67: 998-1003
[Abstract][Full Text]
Kobayashi, S., Kawata, T., Kimura, A., Miyamoto, K., Katayama, K., Yamatsu, I., Rossignol, D. P., Christ, W. J., Kishi, Y.
(1998). Suppression of Murine Endotoxin Response by E5531, a Novel Synthetic Lipid A Antagonist. Antimicrob. Agents Chemother.
42: 2824-2829
[Abstract][Full Text]
Greisman, S.E., Johnston, C.A.
(1997). Review: Evidence against the hypothesis that antibodies to the inner core of lipopolysaccharides in antisera raised by immunization with enterobacterial deep-rough mutants confer broad-spectrum protection during Gram-negative bacterial sepsis. Innate Immunity
4: 123-153
[Abstract]
Morrison, D. C.
(1995). Editorial. Innate Immunity
2: 311-312
Lagrange, P.H., Blanchard, H.S., Felten, A.
(1995). Review: Bacterial endotoxin and the human monoclonal antibody HA-IA: specificity, potential mechanisms of action, and limits to its effectiveness. Innate Immunity
2: 371-386
[Abstract]
Rabinovici, R., Neville, L.F., Feuerstein, G.
(1995). Current understanding of sepsis: criticism and a proposal. Innate Immunity
2: 163-168
[Abstract]
Fisher, C.J. JR
(1995). Can second-generation versions of existing therapeutics be successful in clinical trials of sepsis?. Innate Immunity
2: 227-232
[Abstract]
Porat, R., Paddock, H.N., Cominelli, F., Marra, M.N., Scott, R.W., Schwaitzberg, S.D., Dinarello, C.A.
(1995). Effects of bactericidal/permeability-increasing protein on endotoxin-induced fever and Escherichia coli-induced shock in rabbits. Innate Immunity
2: 9-18
[Abstract]
Field, S.K., Morrison, D.C.
(1994). A hamster anti-idiotype monoclonal antibody, mimicking the inner-core region of Gram-negative bacterial lipopolysaccharide (LPS), stimulates LPS inner-core-specific serum antibodies in hamsters. Innate Immunity
1: 120-130
[Abstract]
Novogrodsky, A, Vanichkin, A, Patya, M, Gazit, A, Osherov, N, Levitzki, A
(1994). Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors. Science
264: 1319-1322
[Abstract]
Cross, A.S., Opal, S.
(1994). Minireview: Therapeutic intervention in sepsis with antibody to endotoxin: is there a future?. Innate Immunity
1: 57-69
[Abstract]
Parrillo, J. E.
(1993). Pathogenetic Mechanisms of Septic Shock. NEJM
328: 1471-1478
[Full Text]
Pizzo, P. A.
(1993). Management of Fever in Patients with Cancer and Treatment-Induced Neutropenia. NEJM
328: 1323-1332
[Full Text]
Gorman, S. E., Plaisance, K.
(1991). Application of Products Produced Through Biotechnology in Infectious Diseases. Journal of Pharmacy Practice
4: 103-116
Wakeford, J. H., Hardin, T. C.
(1991). Sepsis. Journal of Pharmacy Practice
4: 269-280
Sanchez-Cantu, L., Rode, H. N., Christou, N. V.
(1989). Endotoxin Tolerance Is Associated With Reduced Secretion of Tumor Necrosis Factor. Arch Surg
124: 1432-1436
[Abstract]
Dunn, D. L., Priest, B. P., Condie, R. M.
(1988). Protective Capacity of Polyclonal and Monoclonal Antibodies Directed Against Endotoxin During Experimental Sepsis. Arch Surg
123: 1389-1393
[Abstract]
Courtney Broaddus, V., Berthiaume, Y., Biondi, J. W., Matthay, M. A.
(1987). Analytic Reviews : Hemodynamic Management of the Adult Respiratory Distress Syndrome. J Intensive Care Med
2: 190-213
[Abstract]
Dunn, D. L., Ewald, D. C., Chandan, N., Cerra, F. B.
(1986). Immunotherapy of Gram-negative Bacterial Sepsis: A Single Murine Monoclonal Antibody Provides Cross-Genera Protection. Arch Surg
121: 58-62
[Abstract]
Bannerman, D. D., Tupper, J. C., Ricketts, W. A., Bennett, C. F., Winn, R. K., Harlan, J. M.
(2001). A Constitutive Cytoprotective Pathway Protects Endothelial Cells from Lipopolysaccharide-induced Apoptosis. J. Biol. Chem.
276: 14924-14932
[Abstract][Full Text]
