Effect of linezolid on cytokine production capacity and plasma endotoxin levels in response to lipopolysaccharide stimulation of whole blood.
The purpose of this study was to assess lipopolysaccharide (LPS)-stimulated cytokine production in the presence of linezolid (LZD) in comparison with the drug effect on the plasma endotoxin level. Peripheral venous whole-blood samples collected from five healthy subjects were stimulated with 10 microg/ml of LPS. LZD was then added to the LPS-stimulated blood samples at concentrations of 0, 2, 4, and 15 microg/ml , followed by incubation for 24 h at 37 degrees C in a 5% CO(2)-95% air atmosphere. Supernatants of the resultant cultures were assayed to determine the levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, and endotoxin. Significant decreases in the levels of TNF-alpha and IFN-gamma were observed in the LZD 2, 4, and 15 microg/ml groups as compared with that in the 0 microg/ml group (Dunnett's procedure; P < 0.05). The level of IL-10 tended to increase irrespective of the LZD concentration; however, no significant intergroup differences were observed [analysis of variance (ANOVA); P = 0.68]. No significant decrease of the endotoxin level was observed in the LZD 2, 4, or 15 microg/ml groups as compared with that in the 0 microg/ml group, with no significant intergroup differences (ANOVA; P = 0.83). No change in the MCP-1 levels was observed irrespective of the LZD concentration (ANOVA; P = 0.82). To conclude: (1) it appears possible that LZD inhibits the production of INF-gamma and TNF-alpha to a limited extent; (2) LZD did not exert any inhibitory effect on endotoxin production by bacteria, while suppressing cytokine production. The results indicate that LZD may have a significant role in saving the lives of patients with sepsis.
Takahashi
Gaku
G
Department of Critical Care Medicine, Iwate Medical University, School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
Sato
Nobuhiro
N
Yaegashi
Yasunori
Y
Kojika
Masahiro
M
Matsumoto
Naoya
N
Kikkawa
Tomohiro
T
Shozushima
Tatsuyori
T
Akitomi
Shinji
S
Aoki
Kiichi
K
Ito
Naoko
N
Hoshikawa
Koichi
K
Suzuki
Yasushi
Y
Inoue
Yoshihiro
Y
Wakabayashi
Go
G
Endo
Shigeatsu
S
D000081:Acetamides / Q000494:pharmacology*; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000494:pharmacology; D001769:Blood / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004731:Endotoxins / Q000097:blood*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D000069349:Linezolid; D008070:Lipopolysaccharides / Q000494:pharmacology*; D023303:Oxazolidinones / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
D000081:Acetamides; D000890:Anti-Infective Agents; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D023303:Oxazolidinones; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D000069349:Linezolid