Journal article
Treatment of toxic shock syndrome with endotoxin-neutralizing antibody
The Journal of surgical research, Vol.46(6), pp.527-531
1989
DOI: 10.1016/0022-4804(89)90014-0
PMID: 2733415
Abstract
The enhancement of host susceptibility to endotoxin (lipopolysaccharide, LPS) by toxic shock syndrome toxin-1 (TSST-1) is an important mechanism in the pathogenesis of toxic shock syndrome. In these studies, we sought to determine whether an endotoxin-neutralizing monoclonal antibody could be useful in the treatment of toxic shock syndrome. We isolated a murine monoclonal hybridoma (3-H3) which secreted monoclonal antibody (mAb) specific for
Escherichia coli 0111:B4 LPS. Spleen cells cocultured with
E. coli 0111:B4 LPS demonstrated up to a 60% decrease in mitogenic activity in the presence of 3-H3 mAb, but not control mAb, demonstrating that this antibody neutralized endotoxin
in vitro. Rabbits pretreated with 3-H3 mAb or control mAb were injected intradermally with
E. coli 0111:B4 LPS. One day later rabbits received
E. coli 0111:B4 LPS intravenously to elicit the dermal Shwartzman reaction. Rabbits pretreated with 3-H3 mAb did not develop this reaction (0/6) compared to animals pretreated with control mAb (5/6), demonstrating that this antibody neutralized endotoxin
in vivo (
P < 0.05). When this antibody was evaluated in a rabbit model of lethal toxic shock syndrome, rabbits pretreated with antibody demonstrated greater survival (8/14) than saline control animals (1/10) after challenge with TSST-1 and
E. coli 0111:B4 LPS (
P < 0.05). Since the suspicion exists that low levels of endogenous LPS may potentiate TSST-1 activity during clinical toxic shock syndrome, we hypothesized that endotoxin-neutralizing antibodies could be useful in the treatment of this lethal disease process.
Details
- Title: Subtitle
- Treatment of toxic shock syndrome with endotoxin-neutralizing antibody
- Creators
- Brian P Priest - Department of Surgery, Division of Surgical Infectious Diseases, University of Minnesota, Minneapolis, Minnesota 55455 USAPatrick M Schlievert - Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455 USADavid L Dunn - Department of Surgery, Division of Surgical Infectious Diseases, University of Minnesota, Minneapolis, Minnesota 55455 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of surgical research, Vol.46(6), pp.527-531
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0022-4804(89)90014-0
- PMID
- 2733415
- ISSN
- 0022-4804
- eISSN
- 1095-8673
- Language
- English
- Date published
- 1989
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984002379002771
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