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.

Keywords

SepsisPlaceboTumor necrosis factor alphaCytokineMedicineMonoclonal antibodyImmunologyInterleukin 6Septic shockInternal medicineAntibodyLipopolysaccharideInterleukinGastroenterologyPathology

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Publication Info

Year
1992
Type
article
Volume
166
Issue
6
Pages
1367-1374
Citations
107
Access
Closed

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Cornelis H. Wortel, M A von der Möhlen, S J van Deventer et al. (1992). Effectiveness of a Human Monoclonal Anti-Endotoxin Antibody (HA-1A) in Gram-Negative Sepsis: Relationship to Endotoxin and Cytokine Levels. The Journal of Infectious Diseases , 166 (6) , 1367-1374. https://doi.org/10.1093/infdis/166.6.1367

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DOI
10.1093/infdis/166.6.1367