Effects of genistein administration on cytokine induction in whole-body gamma irradiated mice.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in military and civilian populations associated with possible exposure to ionizing radiation. We previously demonstrated that a single subcutaneous (sc) administration of genistein at a non-toxic dose provided protection against acute radiation injury and that the radioprotective effects were associated with multilineage, hematopoietic progenitor cell recovery. The purpose of this study was to determine whether hematopoietic recovery was preceded by cytokine induction. In mice treated with sc genistein 24 h before irradiation (7 Gy 60Co), we quantified serum cytokine levels by multiplex Luminex and also investigated a larger number of cytokines using cytokine arrays. Genistein administration stimulated serum granulocyte-colony stimulating factor (G-CSF) 4h and 24h after sham irradiation or gamma-irradiation. Interleukin-6 (IL-6) was significantly increased in genistein-treated animals 4h after irradiation. Because G-CSF and IL-6 are important hematopoietic factors, these results support our hypothesis that the previously observed radioprotective efficacy by genistein may be a result of early recovery of hematopoietic cells due to enhanced production of G-CSF and IL-6.