Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels

J Infect Dis. 1992 Dec;166(6):1367-74. doi: 10.1093/infdis/166.6.1367.

Abstract

Gram-negative sepsis is caused by endotoxin-induced release of tumor necrosis factor (TNF) and other cytokines. HA-1A is a human monoclonal antibody that binds specifically to endotoxin. HA-1A should prevent death in endotoxemic patients and reduce serum levels of TNF and interleukin-6 (IL-6). This hypothesis was tested in 82 septic patients who were randomly allocated to receive a single intravenous 100-mg dose of HA-1A or placebo. Pretreatment endotoxemia was detected in 27 patients (33%). Death occurred within 28 days of treatment in 8 (73%) of 11 placebo recipients and in 5 (31%) of 16 HA-1A recipients (P = .02). The median decrease in serum TNF level 24 h after treatment was 12 ng/L in patients given HA-1A and 0 ng/L in placebo recipients (n = 65; P = .04). For IL-6, this was 204 ng/L in patients given HA-1A and 44 ng/L in placebo recipients (n = 67; P = .4). Thus, HA-1A reduces mortality in septic patients with endotoxemia and lowers serum TNF levels.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bacteremia / mortality
  • Bacteremia / therapy
  • Cytokines / blood*
  • Endotoxins / blood
  • Endotoxins / immunology*
  • Gram-Negative Bacterial Infections / mortality
  • Gram-Negative Bacterial Infections / therapy*
  • Humans
  • Immunoglobulin M / therapeutic use*
  • Interleukin-6 / blood
  • Middle Aged
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Endotoxins
  • Immunoglobulin M
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • nebacumab