[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
November 1988

Protective Capacity of Polyclonal and Monoclonal Antibodies Directed Against Endotoxin During Experimental Sepsis

Author Affiliations

From the Department of Surgery, University of Minnesota, Minneapolis.

Arch Surg. 1988;123(11):1389-1393. doi:10.1001/archsurg.1988.01400350103016

• Both monoclonal antibody (MAb) and polyclonal antibody (PAb) directed against the shared core/lipid A region of lipopolysaccharide (LPS) (endotoxin) provide protection during experimental gram-negative bacterial sepsis. Although these preparations have not been compared, clinical trials administering either preparation to septic patients have been instituted. The core/lipid A region of LPS represents an antigenic domain common to many, if not all, gram-negative microbes, and thus represents an ideal target site for antibody binding. We sought to determine (1) the protective capacity of similarly reactive IgG anti—core LPS/lipid A MAbs and PAbs, (2) whether the timing of administration was important, and (3) whether either would act additively with antimicrobial agents. Antibody was administered intravenously to outbred mice, and Escherichia coli 0111:B4 was then administered intravenously or intraperitoneally with hemoglobin. Monoclonal antibodies and PAbs were equally protective, and protection was maximized by pretreatment, although the effect extended to four hours after bacterial challenge. Both MAbs and PAbs acted in concert with gentamicin hydrochloride to further reduce lethality. We concluded that MAbs and PAbs were equally protective and that clinical utility may eventually be dictated by ease and cost of antibody production.

(Arch Surg 1988;123:1389-1393)

Dunn DL:  Immunotherapeutic advances in the treatment of gram-negative bacterial sepsis . World J Surg 1987;11:233-240.Article
Dunn DL:  Vaccines and antibody immunotherapy in surgical patients . Am J Surg 1987;153:409-416.Article
Dunn DL:  Antibody immunotherapy of gram-negative bacterial sepsis . Pharmacotherapy 1987;7:S31-S35.
Kreger BE, Craven DE, McCabe WR:  Gram-negative bacteremia: IV Re-evaluation of clinical features and treatment in 612 patients . Am J Med 1980;68:344-355.Article
Bryan CS, Reynolds KL, Brenner ER:  Analysis of 1186 episodes of gram-negative bacteremia in non-university hospitals: The effects of antimicrobial therapy . Rev Infect Dis 1983;5:629-638.Article
Ledingham IM, McCardle CS:  Prospective study of the treatment of shock . Lancet 1978;1:1194-1197.Article
McCabe WR, Bruins SC, Craven DE, et al:  Cross-reactive antigens: Their potential for immunization-induced immunity to gram-negative bacteria . J Infect Dis 1977;136:S161-S166.Article
Braude AI, Ziegler EJ, Douglas H, et al:  Antibody to cell wall glycolipid of gram-negative bacteria: Induction of immunity to bacteremia and endotoxemia . J Infect Dis 1977;136:S167-S173.Article
Dunn DL, Mach PA, Cerra FB:  Monoclonal antibodies protect against lethal effects of gram negative bacterial sepsis . Surg Forum 1983;34:142-144.
Dunn DL, Bogard WC, Cerra FB:  Efficacy of type specific and cross reactive murine monoclonal antibodies directed against endotoxin during experimental sepsis . Surgery 1985;98:283-289.
Kirkland TN, Ziegler EJ:  An immunoprotective monoclonal antibody to lipopolysaccharide . J Immunol 1984;132:2590-2592.
Dunn DL, Ewald DP, Chandan N, et al:  Immunotherapy of gram-negative bacterial sepsis: A single murine monoclonal antibody provides cross-genera protection . Arch Surg 1986;121:58-62.Article
Luderitz O, Staub AM, Westphal O:  Immunochemistry of O and R antigens of Salmonella and related Enterobacteriaceae . Bacteriol Rev 1966; 30:192-225.
Dunn DL, Mach PA, Condie RM, et al:  Anti-core endotoxin F(ab')2 equine immunoglobulin fragments protect against lethal effects of gram negative bacterial sepsis . Surgery 1984;96:440-446.
Dunn DL, Ferguson R:  Immunotherapy of gram-negative bacterial sepsis: Enhanced survival in a guinea pig model by use of rabbit antiserum to Escherichia coli J-5 . Surgery 1982;92:212-219.
Dunn DL:  Antibody immunotherapy of gram-negative bacterial sepsis in an immunosuppressed animal model . Transplantation 1988;425:424-428.Article
Reed LJ, Muench H:  A simple method of estimating fifty percent endpoints . Am J Hygiene 1938;27:493-497.
Dunn DL, Bogard WC Jr, Cerra FB:  Enhanced survival during murine gram-negative bacterial sepsis by use of a murine monoclonal antibody . Arch Surg 1985;120:50-53.Article
Ziegler EJ, McCutchan JA, Fierer J et al:  Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli . N Engl J Med 1982;307:1225-1230.Article
McCutchan JA, Wolf JL, Ziegler EJ, et al:  Ineffectiveness of single-dose human antiserum to core glycolipid (E coli J5) for prophylaxis of bacteremic, gram-negative infections in patients with prolonged neutropenia . Schweiz Med Wochenschr 1983;113S:40-45.
Lachman E, Pitsoe SB, Gaffin SL:  Anti-lipopolysaccharide immunotherapy in management of septic shock of obstetric and gynecological origin . Lancet 1984;1:981-983.Article
Baumgartner JD, McCutchan JA, Van Melle G, et al:  Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid . Lancet 1985;1:59-63.Article