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 m odulate intracellular calcium activity, a critical component in the pr iming and activation of macrophages and polymorphonuclear leukocytes, We hypothesized that taurolidine may function to enhance immune activi ty in these cells, The aim of this study was to investigate the immuno logical effects of taurolidine and correlate findings with survival af ter 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 poi nt survival. Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, Peritoneal macrophage s (PMOs) were assessed for O-2-, NO, tumor necrosis factor-alpha (TNF- alpha), CD11b, phagocytosis, and PMN influx, O-2-. TNF-alpha, CD11b ex pression, and phagocytosis were significantly increased in the tauroli dine group. Study 3: PMOs were cultured in vitro +/-0.5 mg/ml taurolid ine and PMO antimicrobial. function assessed (O-2-, NO, TNF-alpha, and phagocytosis), O-2-, TNF-alpha, and phagocytosis were significantly i ncreased, whereas NO was reduced, Study 4: PMOs were also cultured wit h taurine (0.5 mg/ml), Similar increase in O-2-, TNF-alpha, and phagoc ytosis were identified, Intracellular PMO [Ca2+] was also assessed and increases in free, unbound intracellular [Ca2+] occurred after taurin e culture, Thus, in addition to its bactericidal and antilipopolysacch aride activity, taurolidine primes PMOs for enhanced antimicrobial act ivity and these effects appear mediated by the amino acid taurine.