Antibiotic-induced bacterial killing stimulates tumor necrosis factor-α release in whole blood

Moshe Arditi*, William Kabat, Ram Yogev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Rapid lysis of gram-negative bacteria is associated with considerable release of free endotoxin. Production of tumor nerosis factor (TNF) from adult whole blood ex vivo in response to bacterial products generated during antibiotic killing of Haemophilus influenzae type b (Hib) was investigated. Heparinized whole blood released TNF in a dose-dependent fashion in response to purified lipooligosaccharide of Hib. Bacteria (104-107 cfu/mL) were placed into a Transwell filter insert (0.1 µm) and incubated with whole blood in the presence of various antibiotics. Exposure to ceftriaxone resulted in significantly greater release of TNF during killing of Hib than did exposure to imipenem, despite similar degrees of bacterial killing at 6 h. Polymyxin B inhibited the ceftriaxone-induced TNF release by 97%–99%, indicating that free endotoxin was the predominant stimulus for the increase in TNF release in this system. These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem.

Original languageEnglish (US)
Pages (from-to)240-244
Number of pages5
JournalJournal of Infectious Diseases
Volume167
Issue number1
DOIs
StatePublished - Jan 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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