Effects of antimicrobial agents on spontaneous and endotoxin-induced cytokine release of human peripheral blood mononuclear cells.
Because the immunomodulatory effects of antibiotics could possibly influence the degree of the systemic and local response to infection, knowledge of their intrinsic influence on the host's inflammatory response appears to be essential. Therefore, this study investigated the effects of frequently used antimicrobial agents (beta-lactams, quinolones gentamicin, vancomycin and metronidazole) on the in-vitro tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production of isolated human peripheral blood mononuclear cells (PBMNC), cultured with or without endotoxin, in comparison with those effects obtained in a whole-blood assay system. In the presence of ciprofloxacin, ofloxacin, gentamicin, vancomycin, and metronidazole, a significant inhibition of the endotoxin-stimulated TNF-alpha production of human peripheral blood mononuclear cells (PBMNC) was found at therapeutic levels. Only ofloxacin showed a significant inhibitory influence on the endotoxin-induced IL-6 production of PBMNC. In the whole-blood assay, significant effects were not detectable. None of the antibiotics showed cytotoxicity. It is concluded that, at present, the direct immunological effects of antibiotics should be interpreted carefully with regard to the experimental conditions, and regardless of the therapeutic implications. To assess the potential direct immunomodulatory effect of antimicrobial agents, different cell culture procedures should be used.
Department of Trauma Surgery, University Hospital Mannheim, Clinical Faculty of Medicine, Ruprecht-Karls University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Ulrich
U
Krehmeier
Mark
M
Bardenheuer
Gregor
G
Voggenreiter
Udo
U
Obertacke
Fritz U
FU
Schade
Matthias
M
Majetschak
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha