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Infect. Immun., Jun 1995, 2236-2242, Vol 63, No. 6
JM Prins, EJ Kuijper, ML Mevissen, P Speelman and SJ van Deventer
The concentration and accessibility of endotoxin can increase following
antibiotic killing of gram-negative bacteria. There are indications that
antibiotics may differ in this respect. We measured endotoxin levels in
RPMI 1640 and tumor necrosis factor alpha (TNF-alpha) and interleukin-6
production in whole blood ex vivo after exposure of log- phase Escherichia
coli to antibiotics belonging to different classes, in a final
concentration of 0.5, 5, or 50 times the MIC. After 4 h of incubation at 50
times the MIC, ceftazidime and ciprofloxacin treatment resulted in levels
of endotoxin, TNF-alpha, and interleukin-6 significantly higher than those
of imipenem and gentamicin (P < 0.001). Similar differences in cytokine
induction were measured after 8 h of incubation. At 0.5 times the MIC, the
differences between the antibiotics in measured endotoxin and cytokine
levels were small, with levels comparable to the levels in untreated
cultures. Polymyxin B and, to a lesser degree, recombinant
bactericidal/permeability-increasing protein 21 (rBPI-21) were found to be
potent inhibitors of TNF-alpha release, supporting the concept that the
differences between the antibiotics in cytokine production were indeed due
to differences in amounts of biologically active endotoxin. The presence of
serum from patients suffering from untreated sepsis decreased TNF-alpha
production significantly, in a concentration-dependent manner.
Copyright © 1995, American Society for Microbiology
Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum
Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
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