IGF‑1 may predict the severity and outcome of patients with sepsis and be associated with microRNA‑1 level changes

Abstract

IGF-1 functions as an anti-oxidative stress molecule and some critical patients with sepsis have a lower level of serum IGF-1. However, the association between IGF-1 and the severity or prognosis of sepsis remains unclear. This study aimed to elucidate the relationship between serum IGF-1 levels and the severity and prognosis of sepsis, and the possible mechanism was analyzed. Clinical characteristics of patients with sepsis were recorded and analyzed. Serum IGF-1 levels and micro (mi)RNA-1 levels were tested using radioimmunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively. The A549 cell line and HKC cell line were cultured in vitro and exposed to H2O2 with or without IGF-1 treatment. Cell death was detected by analyzing cell death markers via ELISA kits, and miRNA-1 levels were detected after H2O2 exposure using RT-qPCR analysis. miRNA-1 in cells was upregulated by transfection and IGF‑1 mRNA was detected to determine its relationship with miRNA-1. Once again, cell ELISA kits were used to analyze cell death markers after transfection. Serum IGF-1 levels were reduced in patients with sepsis, whereas miRNA-1 levels were higher (P<0.05 vs. healthy control). Patients in the septic shock subgroup or dead patients had the lowest IGF-1 levels and the highest miRNA-1 levels (P<0.05 vs. sepsis and severe sepsis). IGF-1 levels were inversely proportional to the miRNA-1 level. In vitro, IGF-1 reduced the cell death caused by H2O2. miRNA-1 transfection effectively increased the sensitivity of cells to H2O2 damage by reducing the expression of IGF-1, which was able to prevent cells from injury caused by H2O2. The transfection of negative control miRNA did not influence the level of IGF-1 miRNA and the sensitivity to H2O2 damage. In conclusion, low IGF-1 levels in patients with sepsis may predict increased severity of the condition and poor prognosis. The possible mechanism is that the excessive miRNA-1 levels reduce IGF-1 levels, resulting in insufficient anti-oxidative action by IGF-1 which increases the injury caused by oxidative stress in patients with sepsis.