Radiation protection effect of rhIL-12 on monkey hematopoietic system

Abstract

This study was aimed to investigate the radioprotective effects of recombinant human interleukin-12 (rhIL-12) on monkey hematopoietic system, and to provide experimental evidence for future clinical prophylaxis and treatment for patients who suffered from acute radiation syndrome. In in vitro study, the effect of rhIL-12 in different concentrations (0, 1, 5, 25, 125 and 625 ng/ml) on colony forming capacity of human or monkey bone marrow-derived mononuclear cells was examined in methylcellulose H4434 medium. In in vivo study, the acute radiation syndrome model was established in 11 Rhesus monkeys which received lethal total body irradiation by 6 Gy (60)Co γ in single time irradiation. The irradiated monkeys were randomly divided into 3 subgroups: control group (n = 4) which received subcutaneous PBS injection, rhIL-12 single-dose group (n = 3) which received subcutaneous single injection of rhIL-12 (4 µg/kg) at 2 h after irradiation, and multiple-dose group (n = 4) which received subcutaneous injection of rhIL-12 (1 µg/kg per injection) at 2 h, day 3, 6 and 9 after irradiation respectively. Peripheral blood cells were counted before and after irradiation every other day. The survival status of animals were observed daily. In vitro test results showed that different concentrations of rhIL-12 obviously promoted human and healthy monkeys' bone marrow mononuclear cells to form various hematopoietic progenitor cell colonies, especial CFU-E and CFU-GM. All animals in control group died within 22 d after lethal total body irradiation, average survival time was (20.3 ± 1.2) d. Only one monkey in multiple-dose group died due to anemia on day 17. All monkeys in single-dose group survived. Compared with control group, rhIL-12-administrated monkeys' white blood cell count, hemoglobin level, platelet and reticulocyte counts showed faster recovery from high dose radiation. It is concluded that the rhIL-12 treatment can promote the bone marrow hematopoietic stem/progenitor cell colony formation in vitro and protect lethally-irradiated monkeys. There is an obvious therapeutic effect of rhIL-12 on monkeys suffered from bone marrow failure caused by severe acute radiation exposure.