The effects of electroacupuncture on TH1/TH2 cytokine mRNA expression and mitogen-activated protein kinase signaling pathways in the splenic T cells of traumatized rats

Kun Wang, Huaxing Wu, Guonian Wang, Mingming Li, Zhaodi Zhang, Guangying Gu
Anesthesia and Analgesia 2009, 109 (5): 1666-73

BACKGROUND: Surgical trauma contributes to postoperative immune suppression, which is associated with an increased susceptibility to subsequent infections. Electroacupuncture (EA) can alleviate pain and exert immunoregulatory effects. However, the mechanism underlying the immnuomodulation effects of EA is not fully elucidated. Therefore, we investigated the effects of EA on T helper (Th)1/Th2 cytokine production and mRNA expression and evaluated the signaling regulatory mechanism of EA effects.

METHODS: Rats were divided into four groups (n = 24 each): control, trauma, trauma (T) + sham EA, and T + EA. EA was applied to Zusanli (ST36) and Lanwei (Extra37) acupoints at 20 min after surgery for 30 min, and then performed once a day on postoperative days 1-5. Splenic T cells were isolated and the production and mRNA expression of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 were assayed. The activation of mitogen-activated protein kinase and the DNA binding activity of nuclear factor (NF)-kappaB and activator protein (AP)-1 were examined.

RESULTS: Paw withdrawal threshold and paw withdrawal latency were significantly increased in the T + EA group compared with the trauma group from postoperative day 1 (paw withdrawal threshold: 5.8 +/- 0.7 vs 3.0 +/- 0.7 g; paw withdrawal latency: 7.0 +/- 0.8 vs 4.5 +/- 0.5 s; P < 0.001) to day 5 (9.0 +/- 0.6 vs 5.5 +/- 0.6 g; 12.0 +/- 1.3 vs 7.0 +/- 0.8 s; P < 0.001). Th1 cytokine (IL-2 and interferon-gamma) production and mRNA expression in splenic T cells of traumatized rats were significantly decreased on postoperative day 3 (P < 0.001, trauma group versus control group), whereas Th2 cytokine (IL-4 and IL-10) production and mRNA expression were increased (P < 0.001). This was accompanied with a significant depression in the activity of extracellular-regulated protein kinase (ERK)1/2, p38, NF-kappaB, and AP-1 (P < 0.001, trauma group versus control group). EA administration increased Th1 cytokine protein and mRNA expression, suppressed Th2 cytokine protein and mRNA expression (P < 0.05, T + EA group versus trauma group), and increased the activity of ERK1/2, p38, NF-kappaB, and AP-1 (P < 0.001, T + EA group versus trauma group).

CONCLUSIONS: EA regulates a balance between Th1 and Th2 cytokines at protein and mRNA levels in splenic T cells, and, at least in part, involves the signaling pathways of ERK1/2, p38, NF-kappaB, and AP-1. The findings suggest that EA may improve immune suppression after surgical trauma.

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