The Hematopoietic and Immunomodulatory Effect of rhIL-12 for Liver Cancer

Abstract

Purpose: To explore the effect of rhIL-12 on the number of the blood cells and CD4/8+ T, CD45+ leukocytes, and CD56+ NK cells in liver cancer patients following radiation therapy. Methods: We selected forty liver cancer patients who carried out by cyber knife (the patients were given 5 Gy every time for 5 times continuously) to observe the size of the tumor. After thirty hours, rhIL-12 was injected into the liver cancer patients via subcutaneous at the concentration of 50 ng/kg, 100 ng/kg, 200 ng/kg and 300 ng/kg in different patients, respectively. And there were ten patients in the four groups, respectively. The twenty patients who were selected from the hospital without rhIL-12 treatment were used as controls. All the blood cells were collected from different groups on day 0, hour 12, day 7, day 14, day 21 and day 28 after rhIL-12 treatment, respectively. The full number of blood cells in every group was analyzed by ELISA. The number of CD4/8+ T, CD45+ leukocytes, and CD56+ NK cells were detected by Flow Cytometry. After one month with rhIL-12 treatment, ECOG and WHO were used to evaluate the prognosis of liver cancer. Results: In present study, we found that the number of blood cells was significantly decreased on day 0 - day 3, while recovered from day 7 - day 14 and down-regulated on day 21 after rhIL-12 treatment. The number of CD4/8+ T, CD45+ leukocytes, and CD56+ NK cells was elevated with any concentration of rhIL-12. Furthermore, results showed that number of white blood cells was obviously higher than in patients without rhIL-12 treatment (P < 0.05). However, there was no significant difference of erythrocyte and platelet, between groups treated with rhIL-12 and control groups. In addition, the immune cells including CD4/8+ T, CD45+ leukocytes, and CD56+ NK cells were reduced on day 0 - day 3, recovered from day 7, and then decreased from day 21 in rhIL-12 treatment groups related to control groups (P < 0.05). Furthermore, studies showed that five patients developed symptoms of fever, bilirubin increased and liver dysfunction with the dose of 300 ng/kg. So we found that the safe and well-tolerated human dose of 200 ng/kg is within this efficacious range based on exposure parameters through the research. Higher ECOG and WHO scores were observed in rhIL-12 treatment groups compared to control groups (P = 0.025, P = 0.044, respectively). Conclusion: Our results suggested that rhIL-12 could recover the liver cancer induced aberrant blood cell number and CD4/8+ T, CD45+ leukocytes, and CD56+ NK cells , which may be an effective method to alleviate the progress of liver cancer and played an important role in treating liver cancer.