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Minireview: Therapeutic intervention in sepsis with antibody to endotoxin: is there a future?

Department of Bacterial Disease, Walter Reed Army Institute of Research, Washington DC, USA, Division of Infectious Diseases, Memorial Hospital of Rhode Island, Department of Medicine, Brown University School of Medicine, Providence, RI, USA

S. Opal

Department of Bacterial Disease, Walter Reed Army Institute of Research, Washington DC, USA, Division of Infectious Diseases, Memorial Hospital of Rhode Island, Department of Medicine, Brown University School of Medicine, Providence, RI, USA

Within the last 24 months a number of studies that tested the efficacy of immunologic reagents in the treatment of sepsis were concluded. Among these reports were 4 studies^1-4 completed on 2 anti-endotoxin monoclonal antibodies (MAb, HA-1A and E-5). These clinical trials did not generate data sufficient to support product licensure. Given the attention and expectations surrounding the anti-endotoxin MAbs, the disappointing results raised the question whether the use of anti-endotoxin antibodies in the treatment of sepsis was still a viable concept.⁵ The question was rendered even more relevant given the decade-old controversy surrounding the efficacy of polyclonal antibodies to endotoxin, particularly antibody to the J5 (Rc chemotype) mutant of Escherichia coli 0111:B4, a conceptual progenitor of the HA-1A and E-5 MAbs.⁶ In this review we shall examine whether anti-endotoxin antibodies may yet offer any therapeutic potential in the treatment of sepsis. It will be our contention that antibodies to core glycolipid will be useful adjuncts to therapy, particularly if used as part of combination immunotherapy.

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