Differences in release of tumor necrosis factor from THP-1 cells stimulated by filtrates of antibiotic-killed Escherichia coli.
Bacterial products, such as endotoxin, activate mononuclear cells to produce tumor necrosis factor (TNF) and other monokines capable of producing host cell injury. THP-1 cell TNF release in response to bacterial products generated during antibiotic killing of Escherichia coli (ATCC 12014) was evaluated. THP-1 is a mature monocytic leukemia cell line that produces TNF in a dose-dependent fashion in response to purified endotoxin. E. coli were incubated in the presence of amikacin, ciprofloxacin, ceftazidime, cefotaxime, aztreonam, or imipenem at concentrations that killed greater than 99.9% of the organisms. Aliquots of these antibiotic-bacterial cultures were added to THP-1 cells, and TNF concentrations were determined by specific immunoassay. Amikacin and imipenem produced rapid bacterial killing and were associated with low TNF levels. Ceftazidime, aztreonam, and cefotaxime killed E. coli at a slower rate and were associated with significant increases in mononuclear cell TNF responses. Ciprofloxacin produced intermediate TNF levels. Differences exist among bactericidal antibodies in their ability to generate products capable of stimulating mononuclear cell TNF release.
Simon
D M
DM
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Koenig
G
G
Trenholme
G M
GM
D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin; D015378:Imipenem; D000583:Amikacin; D002442:Ceftazidime; D001398:Aztreonam; D002439:Cefotaxime