Enhancement of human natural killer cell activity by modified arabinoxylan from rice bran (MGN-3)

Arabinoxylane from rice bran (MGN-3) was examined for its augmentory effect on human NK (NK) cell activity in vivo and in vitro. Twenty-four individuals were given MGN-3 orally at three different concentrations: 15, 30 and 45 mg/kg/day for 2 months. Peripheral blood lymphocyte-NK cell activity was tested by 51Cr release assay against K562 and Raji tumor cells at 1 week, 1 month and 2 months posttreatment and results were compared with baseline NK activity. Treatment with MGN-3 enhanced NK activity against K562 tumor cells at all concentrations used. In a dose-dependent manner, MGN-3 at 15 mg/kg/day increased NK activity after 1 month posttreatment (twofold over control value), while significant induction of NK activity at 30 mg/kg/day was detected as early as 1 week posttreatment (three times control value). NK cell activity continued to increase with continuation of treatment and peaked (fivefold) at 2 months (end of treatment period). Increasing the concentration to 45 mg/kg/day showed similar trends in NK activity, however the magnitude in values was higher than for 30 mg/kg/day. After discontinuation of treatment, NK activity declined and returned to baseline value (14 lytic units) at 1 month. Enhanced NK activity was associated with an increase in the cytotoxic reactivity against the resistant Raji cell line. MGN-3 at 45 mg/kg/day showed a significant increase in NK activity after 1 week (eightfold) and peaked at 2 months posttreatment (27 times that of baseline). Culture of peripheral blood lymphocytes (PBL) with MGN-3 for 16 h demonstrated a 1.3 to 1.5 times increase in NK activity over control value. The mechanism by which MGN-3 increases NK activity was examined and showed no change in cluster of differentiation (CD) 16+ and CD56+ CD3- of MGN-3-activated NK cells as compared with baseline value; a fourfold increase in the binding capacity of NK to tumor cell targets as compared with baseline value; and a significant increase in the production of interferon-γ (340-580 pg/ml) postculture of PBL with MGN-3 at concentrations of 25-100 μg/ml. Thus, MGN-3 seems to act as a potent immunomodulator causing augmentation of NK cell activity, and with the absence of notable side-effects, MGN-3 could be used as a new biological response modifier (BRM) having possible therapeutic effects against cancer.