Effects of anesthetic methods on preserving anti-tumor T-helper polarization following hepatectomy

Abstract

Aim: To investigate the impact of different anesthetic techniques on T-helper (Th) cell subsets in hepatocellular carcinoma (HCC) patients undergoing hepatectomy.

Methods: Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia (G + E; n = 31) or a general anesthesia (G; n = 30) group. Blood samples were obtained the morning before the operation (d0), and on the second (d2) and seventh (d7) day after the operation. Th cell contents were evaluated using flow cytometry, real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: In all 61 patients, Th1 and Th2 cell frequencies, and interferon-γ (IFN-γ) mRNA expression markedly increased on d2, compared to d0. They recovered slightly on d7, and the Th1/Th2 ratio increased markedly on d7, compared with d2. In contrast, Th17, regulatory T cell (Treg), and interleukin-17 (IL-17) levels and FOXP3 mRNA expression showed no significant change on d2, and then markedly decreased on d7. Similarly, plasma IFN-γ concentration on d2 was much higher than that on d0, and then partly recovered on d7. As compared with the G group, in the G + E group, Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7, while Th2, Th17, and Treg cell frequencies were slightly lower on d2, and significantly lower on d7. Consistently, on d7, IFN-γ mRNA and protein levels and the IFN-γ/IL-4 ratio in the G + E group were higher than those in the G group. In contrast, the IL-17 mRNA level, and IL-17 and transforming growth factor-β₁ concentrations in the G + E group were lower than those in the G group.

Conclusion: G + E is superior to G in shifting the Th1/Th2 balance towards Th1, while decreasing Th17 and Treg, potentially benefiting HCC patients by promoting anti-tumor Th polarization.

Keywords: Epidural anesthesia; General anesthesia; Hepatocellular carcinoma; T-helper cell; Tumor resection.

Figures

Figure 1

Circulating T-helper 1 and T-helper 2 frequencies increased on d2 vs d0, and then recovered on d7, while T-helper 17 and regulatory T cell frequencies showed no difference on d2 vs d0, but decreased on d7. A and B: FACS pictures showing T-helper (Th)1/Th2/Th17/Treg frequencies from a representative patient (d0 vs d2, bP < 0.01 for both) (Th1: d0 vs d7, bP < 0.01; d2 vs d7, aP < 0.05; Th2: d2 vs d7, bP < 0.01) (Th17: d2 vs d7, bP < 0.01; Treg: d2 vs d7, aP < 0.05); C: Statistical analyses of results from flow cytometry (n = 61).

Figure 2

Representative FACS pictures of T-helper-cell subsets in the G + E and G group. A: Circulating T-helper (Th) 1 frequencies were higher in the G + E group than those in the G group on d7; B: Th2 frequencies were lower in the G + E group than those in the G group on d2; C and D: Th17 and Treg frequencies were lower in the G + E group than those in the G group on d7. G: General anesthesia; E: Epidural block.

Figure 3

Statistics of T-helper-cell contents as measured by mRNA expression and cytokine levels. A: mRNA expression of interferon (IFN)-γ, interleukin (IL)-4, IL-17 and FoxP3 on d0, d2 and d7; The mRNA expression levels of IFN-γ on d2 were increased compared to that on d0 (d0 vs d2, bP < 0.01), then partly recovered on d7 (d2 vs d7, cP <0.05). IL-4, IL-17 and FOXP3 mRNA expression levels showed no significant differences from d0 to d2, whereas mRNA levels of IL-17 and FOXP3 clearly decreased from d2 to d7 (IL-17: d2 vs d7, cP < 0.05; Treg: d2 vs d7, dP < 0.01); B: Cytokine concentrations of IFN-γ, IL-4, IL-17, IL-10 and transforming growth factor (TGF)-β1 on d0, d2 and d7 (d0 vs d2: aP < 0.05, bP < 0.01, respectively).