Acupuncture, Granulocytes, and Inflammation in the Digestive System

Granulocytes—especially neutrophils—are central players in acute inflammation of the digestive system. During intestinal injury, these leukocytes migrate across vascular endothelial cells into inflamed tissues, contributing to both tissue damage and repair. Recent experimental studies reveal how acupuncture may influence granulocyte activity, reduce excessive inflammation, and protect gastrointestinal function.

1. Strengthening Tight Junctions and Limiting Leukocyte Infiltration

One hallmark of intestinal inflammation is the penetration of leukocytes into damaged mucosa. Electroacupuncture (EA) at ST36 has been shown to:

• Up-regulate tight junction–related proteins such as cadherin, claudin-1, and ZO-1 in colonic tissue.
• Strengthen epithelial barrier integrity and reduce structural disruption.
• Prevent leukocyte migration and infiltration into injured sites in dextran sulfate sodium (DSS)-induced colitis.

These findings suggest that the repair of tight junctions may be one of the important mechanisms by which EA at ST36 reduces gastrointestinal inflammation.

2. Inhibiting MPO Activity and Neutrophil-Driven Inflammation

Myeloperoxidase (MPO), produced by granulocytes, reflects the activation level of polymorphonuclear leukocytes (PMNs) and helps drive a positive feedback loop that further promotes neutrophil activation. Several studies show that EA at lower limb and abdominal acupoints can modulate this process:

• EA at ST36, ST37, ST39, or CV4 decreases MPO activity and lowers inflammatory factors such as TNF-α and IL-6.
• By limiting immune cell infiltration, EA protects smooth muscle structure and function.
• EA increases α-smooth muscle actin (α-SMA) expression and improves gastrointestinal motility in postoperative ileus (POI)–related models.

3. SP6 and Granulocyte-Mediated Peritonitis

Manual acupuncture (MA) at SP6 has shown meaningful anti-inflammatory effects in lipopolysaccharide (LPS)-induced peritonitis models:

• Down-regulating TNF-α and IL-6 in peritoneal fluid.
• Up-regulating anti-inflammatory IL-10.
• Inhibiting MPO activity and alleviating peritoneal inflammation.

These results highlight the ability of SP6 to modulate granulocyte-related inflammation both locally and systemically.

4. Protecting Against Liver Ischemia–Reperfusion Injury

Liver ischemia–reperfusion (I/R) injury is a common clinical complication in surgery and transplantation, and excessive inflammation is a key risk factor. EA at LI4 (Hegu) has been reported to:

• Reduce TNF-α and IL-6 levels in serum and liver tissues.
• Inhibit MPO activity and prevent excessive neutrophil-driven inflammatory responses.
• Help control I/R-associated liver inflammation and tissue damage.

5. Acupoint Specificity and the Importance of Stimulation Frequency

Comparative studies highlight that not all acupoints and stimulation parameters are equivalent in treating digestive inflammatory diseases.

5.1 Acupoint selection

• In POI models, EA at ST36, ST37, ST39, or CV4 provides similar beneficial effects on motility and inflammation.
• In contrast, EA at ST25, CV12 or non-acupoints shows little or no therapeutic effect on POI.

These observations support the concept that lower limb acupoints are more frequently used and effective than local abdominal acupoints in gastrointestinal inflammatory conditions, reflecting meridian-based treatment patterns rather than purely local needling.

5.2 SP6 and acupoint specificity

In peritonitis models, MA at SP6 reduces TNF-α and IL-6 levels in both the peritoneal fluid and brainstem, while MA at non-acupoints only partially prevents IL-6 increase in the brainstem. This suggests strong acupoint specificity for SP6 in treating inflammatory disease.

5.3 Frequency of electroacupuncture

• In POI models, 10 Hz or 30 Hz EA significantly increases gastrointestinal peristalsis and reduces inflammation, with 10 Hz being more effective.
• 2 Hz and 100 Hz EA do not show obvious therapeutic benefits in the same model.
• In colitis models, both 10 Hz and 100 Hz EA at ST36 influence macrophage polarization and inflammatory factor release, but only high-frequency stimulation significantly increases Nrf2/HO-1 levels, indicating an additional mechanism via oxidative stress modulation.

6. Integrated View: How Acupuncture Modulates GI Immune Responses

When the above results are considered together—in models of colitis, peritonitis, POI, and liver I/R injury—acupuncture appears to:

• Regulate gastrointestinal macrophage polarization.
• Reduce mast cell degranulation.
• Inhibit the TLR4/MyD88-mediated NF-κB pathway.
• Decrease pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β.
• Support functional gastrointestinal cells such as interstitial Cajal cells (ICCs) and smooth muscle cells.
• Restore gastrointestinal motility and reduce excessive inflammatory reactions.

Together, these findings highlight acupuncture as a potential system-level modulator of granulocyte-driven inflammation in the digestive tract.

顆粒球（尤其是中性球）是急性消化道發炎中的重要效應細胞。 在腸道受損時，白血球會穿過血管內皮層進入發炎組織，既能協助清除病原體， 卻也常導致額外的組織傷害。近年實驗研究顯示，針灸可以從調節顆粒球活性、 抑制過度發炎與保護腸道功能等多個層面發揮作用。

一、強化緊密連結，減少白血球過度滲入

腸道發炎的一大特徵，是白血球穿透血管與上皮屏障，深入受損黏膜。 研究指出，電針 足三里（ST36） 能：

• 上調結腸緊密連結相關蛋白，包括 cadherin、claudin-1、ZO-1。
• 強化腸道上皮屏障，減少結構鬆動與破損。
• 在 DSS 誘導結腸炎 模型中，降低白血球向受傷部位的遷移與浸潤。

這些結果顯示，修復緊密連結可能是電針足三里減少腸道發炎的重要機制之一。

二、抑制 MPO 與中性球活化，保護腸道平滑肌

顆粒球釋放的 髓過氧化物酶（MPO） 是中性球活化的重要指標， 並可透過自分泌與旁分泌形成促發炎的正回饋迴路。 多項研究顯示，電針下肢與腹部穴位可調節此過程：

• 電針 足三里（ST36）、上巨虛（ST37）、下巨虛（ST39）、關元（CV4） 能降低 MPO 活性，並減少 TNF-α、IL-6 等發炎因子。
• 透過抑制免疫細胞浸潤，保護腸道平滑肌結構與功能。
• 增加 α 平滑肌動蛋白（α-SMA） 的表現，改善腸道蠕動， 對術後腸麻痺（POI）相關模型特別有幫助。

三、三陰交（SP6）與腹膜炎中的顆粒球調節

在脂多糖（LPS）誘導的腹膜炎模型中，手針 三陰交（SP6） 顯示出顯著的抗發炎效果：

• 降低腹膜液中的 TNF-α 與 IL-6。
• 提升抗發炎細胞激素 IL-10。
• 抑制 MPO 活性，減輕腹膜發炎反應。

這說明三陰交在調節顆粒球相關的局部與全身性發炎中，具有高度穴位特異性。

四、合谷（LI4）對肝臟缺血再灌注損傷的保護作用

肝臟缺血再灌注（I/R）損傷是外科手術與移植中常見的臨床難題，過度的發炎 與中性球活化是主要風險因子之一。研究指出，電針 合谷（LI4） 能：

• 降低血清與肝組織中的 TNF-α、IL-6 濃度。
• 抑制 MPO 活性，減少中性球相關的組織攻擊。
• 從而控制 I/R 相關的肝臟急性發炎與組織損傷。

五、穴位特異性與電針頻率：不是「隨便扎一針」就好

有些研究直接比較不同穴位與刺激參數，結果顯示針灸的效果高度依賴選點與頻率。

5.1 穴位選擇的重要性

• 在術後腸麻痺模型中，電針 ST36、ST37、ST39、CV4 對改善蠕動與降低發炎的效果相近。
• 相較之下，電針 天樞（ST25）、中脘（CV12） 或非穴位， 對 POI 則幾乎沒有明顯療效。

這些結果支持「下肢經穴較腹部近位穴更常被使用且更有效」的臨床規律， 反映了循經與適應證的重要性，而非僅看「離病灶最近」。

5.2 三陰交（SP6）的穴位特異性

在腹膜炎模型中，手針三陰交不僅能降低腹膜液中的 TNF-α、IL-6， 也能減少腦幹區域的發炎反應；而針刺非穴位僅能部分阻止腦幹 IL-6 升高， 顯示三陰交在疾病治療上具有明顯的穴位特異性。

5.3 電針頻率的差異

• 在 POI 模型中，10 Hz 與 30 Hz 電針能明顯促進 腸蠕動、減少局部發炎，其中以 10 Hz 效果較佳。
• 2 Hz 與 100 Hz 電刺激則未見明顯療效。
• 在結腸炎模型中，10 Hz 與 100 Hz 電針足三里都能調節巨噬細胞極化與發炎 因子釋放，但只有高頻（100 Hz）明顯提升 Nrf2/HO-1 表現， 顯示其可能同時透過調控氧化壓力發揮作用。

六、整體觀點：針灸如何調節腸道免疫與顆粒球發炎？

綜合結腸炎、腹膜炎、術後腸麻痺與肝臟 I/R 損傷等不同模型，針灸的整體作用 包含：

• 調節腸道巨噬細胞極化，平衡 M1/M2 發炎狀態。
• 減少肥大細胞脫顆粒與相關發炎放大反應。
• 抑制 TLR4/MyD88 介導的 NF-κB 發炎訊號。
• 降低 TNF-α、IL-6、IL-1β 等促發炎細胞激素。
• 保護腸道功能細胞，例如腸道起搏細胞（ICCs）與平滑肌細胞。
• 恢復腸道蠕動與消化道運動功能，減少顆粒球過度活化造成的二次損傷。

這些研究顯示，針灸在顆粒球主導的急性與慢性消化系統發炎中， 具有作為「全身性免疫調節工具」的潛力。