Taurolidine, an analogue of the amino acid taurine, suppresses interleukin 1 and tumor necrosis factor synthesis in human peripheral blood mononuclear cells.
Taurolidine (Geistlich Pharm, AG, Wolhusen, Switzerland), a derivative of the amino acid taurine, is commonly used in some parts of the world as an adjunctive therapy for various infections. Its mechanism of action is thought to be related to its antimicrobial properties, including its ability to interfere with some of the biological activities of endotoxin (lipopolysaccharide, LPS). For example, taurolidine has been shown to protect animals against endotoxic shock and death. In this study we examined the ability of taurolidine to block LPS-induced tumor necrosis factor (TNF) and interleukin 1 (IL-1) synthesis in human peripheral blood mononuclear cells (PBMC) from 27 donors. We observed a dose-dependent reduction in the synthesis of these two cytokines when taurolidine was preincubated with LPS before being added to PBMC. This reduction was independent of the molar ratio of taurolidine to LPS but was related to the concentration of taurolidine present in the PBMC cultures. There was a 80 to 90% reduction in total IL-1 and TNF synthesis induced by LPS at concentrations of taurolidine of 40 to 100 micrograms/mL; the vehicle was without effect. Following a 30-min preincubation with PBMC, taurolidine could be washed from the cells and still suppress cytokine synthesis induced by LPS. Using release of lactic acid dehydrogenase, 100 micrograms/mL of taurolidine was not toxic for PBMC. Taurolidine also reduced IL-1 and TNF synthesis induced by the Staphylococcus aureus-derived toxic shock syndrome toxin-1 as well as that induced by nontoxic heat-killed Staphylococcus epidermidis organisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Bedrosian
I
I
Department of Medicine, New England Medical Center, Boston, MA 02111.
Sofia
R D
RD
Wolff
S M
SM
Dinarello
C A
CA
D000123:Acetyltransferases / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D013654:Taurine / Q000031:analogs & derivatives*; D013829:Thiadiazines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001427:Bacterial Toxins; D007375:Interleukin-1; D013829:Thiadiazines; D014409:Tumor Necrosis Factor-alpha; D013654:Taurine; C012566:taurolidine; D000123:Acetyltransferases; C071936:lipopolysaccharide O-antigen acetyltransferase