Gamma-tocotrienol (GT3), a promising radioprotectant, is shown to protect CD2F1 mice from radiation-induced
neutropenia and
thrombocytopenia when given 24h prior to total-body irradiation. GT3 also is shown to increase white blood cells (WBC) and absolute neutrophil counts (ANC) transiently in peripheral blood. We hypothesized that increases in WBC and ANC may involve stimulation of hematopoiesis possibly by
cytokines and
growth factors. To evaluate the effects of GT3 on hematopoietic system, we measured various
cytokines,
chemokines and
growth factors by
cytokine array and Bio-Plex assays. Both showed strong induction of various
cytokines and
chemokines. GT3 treatment resulted in significant increases in
G-CSF, IL-1α, IL-1β,
IL-6, IL-12p70,
IL-17, MIP-1α, and KC levels.
G-CSF levels increased markedly within 12-24h after administration (5441 pg/ml in GT3-treated groups compared to 17 pg/ml in vehicle control). Most of these
cytokine levels were elevated in the presence or absence of radiation. Time-course analysis of
G-CSF and
IL-6 induction showed that both
cytokines were induced transiently after GT3 administration, and returned to normal levels by 48 h post-administration. For
G-CSF, the peak was observed between 12 and 24h post-administration of GT3; however, the highest levels of
IL-6 were obtained between 6 and 12h. These results demonstrate that GT3 induced high levels of
G-CSF and other inflammatory
cytokines and
chemokines within 24h after administration. Survival studies reported showed that the most efficacious time for administering GT3 was 24h prior to irradiation, possibly because it induced key hematopoietic
cytokines in that time window. These results also suggest a possible role of GT3-induced
G-CSF stimulation in protecting mice from radiation-induced
neutropenia and
thrombocytopenia.