Erb-(IL10)2 ameliorates radiation-induced skin injury through eliminate oxygen free radicals

Objective: Radiation-induced skin injury (RISI) remains a serious concern during radiotherapy. IL-10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation. Methods: We fused Interleukin 10 (IL-10) dimer onto an anti-epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb-(IL10)2. The protective effect and biological activity of Erb-(IL10)2 was measured in model of RISI. Results: Under the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non-IR group (p = 0.0021). The survival rates of HaCaT (p = 0.0038) and WS1 (p = 0.0003) cells were significantly increased after IL-10 treatment. The apoptosis rates of HaCaT (p = 0.0048) and WS1 (p = 0.0074) cells in the IL-10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL-10 fusion protein reduced the level of reactive oxygen in HaCaT (p = 0.0046) and WS1 (p<0.0001) cells compared to the control group. Relatively normal granular mitochondrial morphology was observed in the IL-10 group after 20 Gy X-ray irradiation compared with the NC group. Ater 35 Gy electron radiation, the levels of reactive oxygen species in the skin tissue of C57/B6 mice injected with IL-10 fusion protein were significantly lower than those in the PBS group (p = 0.001). Compared with the PBS group and the other IL-10 groups, the group treated with 0.2 mg/kg IL-10 showed a significant decrease in MDA level (p = 0.0024). Compared with the PBS group, the thickness of the stratum corneum in groups treated with 0.05, 0.1 and 0.2 mg/kg IL-10 decreased, and the skin appendages were well-preserved. In the group treated with 0.2 mg/kg IL-10, the skin tissue structure was still relatively intact, and the masson staining area was smaller than that of the PBS group. Conclusion: IL-10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury. IL-10 has a protective effect on skin cell damage after ionizing radiation irradiation both in vitro and in vivo. Moreover, IL-10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury.