Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels.
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.
Wortel
C H
CH
Department of Gastroenterology, University of Amsterdam, Netherlands.
von der Möhlen
M A
MA
van Deventer
S J
SJ
Sprung
C L
CL
Jastremski
M
M
Lubbers
M J
MJ
Smith
C R
CR
Allen
I E
IE
ten Cate
J W
JW
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016470:Bacteremia / Q000401:mortality / Q000628:therapy; D016207:Cytokines / Q000097:blood*; D004731:Endotoxins / Q000097:blood / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007075:Immunoglobulin M / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D004731:Endotoxins; D007075:Immunoglobulin M; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C068069:nebacumab