Taurolidine, an antilipopolysaccharide agent, has immunoregulatory properties that are mediated by the amino acid taurine.
Taurolidine has bactericidal and antilipopolysaccharide properties. It is broken down into the amino acid taurine, which has been shown to modulate intracellular calcium activity, a critical component in the priming and activation of macrophages and polymorphonuclear leukocytes. We hypothesized that taurolidine may function to enhance immune activity in these cells. The aim of this study was to investigate the immunological effects of taurolidine and correlate findings with survival after a septic challenge in a murine model. Study 1: CD-1 mice underwent cecal ligation and puncture, were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, and studied for end point survival. Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control. Peritoneal macrophages (PM luminal diameters) were assessed for O2-, NO, tumor necrosis factor-alpha (TNF-alpha), CD11b, phagocytosis, and PMN influx. O2-, TNF-alpha, CD11b expression, and phagocytosis were significantly increased in the taurolidine group. Study 3: PM luminal diameters were cultured in vitro +/- 0.5 mg/ml taurolidine and PM luminal diameter antimicrobial function assessed (O2-, NO, TNF-alpha, and phagocytosis). O2-, TNF-alpha, and phagocytosis were significantly increased, whereas NO was reduced. Study 4: PM luminal diameters were also cultured with taurine (0.5 mg/ml). Similar increase in O2-, TNF-alpha, and phagocytosis were identified. Intracellular PM luminal diameter [Ca2+] was also assessed and increases in free, unbound intracellular [Ca2+] occurred after taurine culture. Thus, in addition to its bactericidal and antilipopolysaccharide activity, taurolidine primes PM luminal diameters for enhanced antimicrobial activity and these effects appear mediated by the amino acid taurine.
Watson
R W
RW
Department of Surgery, RCSI, Beaumont Hospital, Dublin, Ireland.
Redmond
H P
HP
Mc Carthy
J
J
Bouchier-Hayes
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005260:Female; D016177:Macrophage-1 Antigen / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010538:Peritonitis / Q000503:physiopathology*; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D013829:Thiadiazines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016177:Macrophage-1 Antigen; D013829:Thiadiazines; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D013654:Taurine; D009569:Nitric Oxide; C012566:taurolidine; D002118:Calcium