BACKGROUND: Recombinant interleukin-2 (rIL-2) immunotherapy is limited by microvascular endothelial cell (EC)-targeted injury. The interaction between rIL-2-activated lymphoid cells and EC is a possible mechanism of this systemic toxicity. Taurine, a beta-amino acid, is known to have several physiologic actions, including the modulation of calcium homeostasis. The aims of this study were to analyze the effects of taurine on rIL-2-activated, lymphocyte-mediated EC and tumor cell cytotoxicity and to investigate the mechanisms of its action. METHODS: IL-2-activated cytotoxicity, mediated by peripheral blood mononuclear cells, against susceptible tumor cell lines and against EC (fresh EC and an EC cell line) in the presence of taurine was assessed. The effects of taurine on lymphocyte [Ca2+]i were assessed by flow cytometry, and the effects of taurine on granzyme activity were assessed by spectrophotometry. RESULTS: The authors' findings indicated that the addition of taurine significantly reduced rIL-2-activated EC cytotoxicity mediated by natural killer cells, without reducing antitumor response. Taurine was also shown to reduce significantly EC lysis mediated by lymphokine-activated killer (LAK) cells, while also significantly increasing tumor cytotoxicity. The authors demonstrated the importance of calcium in the role played by taurine in lymphocyte-mediated cytotoxicity and found that LAK [Ca2+]i following conjugation to EC was enhanced by taurine. They also found that taurine enhanced Ca2+-dependent granzyme exocytosis from LAK cells. CONCLUSIONS: These findings indicate that taurine may play a dual role in rIL-2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity.
BACKGROUND: Recombinant interleukin-2 (rIL-2) immunotherapy is limited by microvascular endothelial cell (EC)-targeted injury. The interaction between rIL-2-activated lymphoid cells and EC is a possible mechanism of this systemic toxicity. Taurine, a beta-amino acid, is known to have several physiologic actions, including the modulation of calcium homeostasis. The aims of this study were to analyze the effects of taurine on rIL-2-activated, lymphocyte-mediated EC and tumor cell cytotoxicity and to investigate the mechanisms of its action. METHODS:IL-2-activated cytotoxicity, mediated by peripheral blood mononuclear cells, against susceptible tumor cell lines and against EC (fresh EC and an EC cell line) in the presence of taurine was assessed. The effects of taurine on lymphocyte [Ca2+]i were assessed by flow cytometry, and the effects of taurine on granzyme activity were assessed by spectrophotometry. RESULTS: The authors' findings indicated that the addition of taurine significantly reduced rIL-2-activated EC cytotoxicity mediated by natural killer cells, without reducing antitumor response. Taurine was also shown to reduce significantly EC lysis mediated by lymphokine-activated killer (LAK) cells, while also significantly increasing tumorcytotoxicity. The authors demonstrated the importance of calcium in the role played by taurine in lymphocyte-mediated cytotoxicity and found that LAK [Ca2+]i following conjugation to EC was enhanced by taurine. They also found that taurine enhanced Ca2+-dependent granzyme exocytosis from LAK cells. CONCLUSIONS: These findings indicate that taurine may play a dual role in rIL-2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity.