M. Ghoneum, ENHANCEMENT OF HUMAN NATURAL-KILLER-CELL ACTIVITY BY MODIFIED ARABINOXYLANE FROM RICE BRAN (MGN-3), International journal of immunotherapy, 14(2), 1998, pp. 89-99
Arabinoxylane from rice bran (MGN-3) was examined for its augmentory e
ffect 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 Cr-51 release assay against K562 and Raji
tumor cells at I week, I 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 af
ter 1 month posttreatment (twofold over control value), while signific
ant induction of NK activity at 30 mg/kg/day was detected as early as
I week posttreatment (three times control value). NK cell activity con
tinued 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 magn
itude 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 I month. Enhanced NK activity was associated with an
increase in the cytotoxic reactivity against the resistant Raji cell l
ine. MGN-3 at 45 mg/kg/day showed a significant increase in NK activit
y after I week (eightfold) and peaked at 2 months posttreatment (27 ti
mes that of baseline). Culture of peripheral blood lymphocytes (PBL) w
ith MGN-3 for 16 h demonstrated a 1.3 to 1.5 times increase in NK acti
vity over control value. The mechanism by which MGN-3 increases NK act
ivity was examined and showed no change in cluster of differentiation
(CD)16(+) and CD56(+) CD3(-) of MGN-5-activated NK cells as compared w
ith baseline value; a fourfold increase in the binding capacity of NK
to tumor cell targets as compared with baseline value; and a significa
nt increase in the production of interferon-gamma (340-580 pg/ml) post
culture of PBL with MGN-3 at concentrations of 25-100 mu g/ml. Thus, M
GN-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 possi
ble therapeutic effects against cancer.