Use of N-acetyl cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2.

摘要: IL-2 therapy can induce marked oxidative stress via reactive oxygen and nitrogen intermediates. Glutathione, the major intracellular reductant, may become rate limiting to cytotoxic lymphocyte activation proliferation under these circumstances. N-Acetyl cysteine (NAc-cys) was used increase glutathione levels during lymphokine-activated killer (LAK) cell by IL-2. Incubation of splenocytes with NAc-cys (0.6 1.0 mM) resulted in significant changes reduced total (92% 58% increase, respectively) at 96 h. These correlated markedly enhanced (threefold) cytolytic effector generation (> fivefold LU/10(6) cells) induced combination exposure itself unexpectedly increased 43%. were synergistic increasing (reduced glutathione: 292% increase; total: 251% increase). Inhibition synthesis, using L-buthionine-(S,R)-sulfoximine reversed effects on glutathione, as well cellular cytotoxicity. This experiment established that required de novo synthesis. In conjunction IL-2/LAK treatment, oral administration (260 900 mg/kg/day for 7 days) significantly decreased tumor progression a refractory s.c. model. A small fraction mice (11 17%) had complete regressions. be useful an adjunct antitumor activity therapy.