In vivo TNF induction by culture supernatants of antibiotic-treated Escherichia coli 07:K1. Role of antibiotic class and concentration

Willem N.M. Hustinx*, Barry J. Benaissa-Trouw, Ingeborg Van Der Tweel, Theo Harmsen, Jan Verhoef, Andy I.M. Hoepelman, Kees A. Kraaijeveld

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Antibiotics may cause an excess release of lipopolysaccharide (LPS) from bacteria and thereby promote the production of tumour necrosis factor (TNF). TNF was measured in the serum of Swiss mice challenged with filtered supernatant of Escherichia coli O7:K1 that had been exposed to various antibiotics in vitro. Expressed as a function of a standardized number of cells remaining after 6 h of exposure to gentamicin, ceftazidime, ciprofloxacin or imipenem, TNF levels associated with antibiotic exposure always exceeded those of controls. However, if differences in the remaining number of bacteria were not taken into account, TNF induction by supernatant of control untreated cultures was greater than that elicited by supernatant from any of the antibiotic-treated cultures. With the exception of imipenem, low-dose antibiotic exposure (0.5 × MIC) invariably induced higher TNF levels than did high-dose exposure (10 × MIC). Considerable antibiotic class- and concentration-related differences were noted. LAL equivalent amounts of LPS released by different antibiotics may diverge in their capacity to induce TNF. Our results do not support the notion that the use of rapidly bactericidal and lytic antibiotics should be avoided.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalInternational Journal of Antimicrobial Agents
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Jan 1996

Keywords

  • Antibiotic-induced endotoxin release
  • Cytotoxicity assay
  • Escherichia coli
  • In vivo tnf induction
  • Lal assay
  • Swiss mice

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