Acupuncture, Macrophages, and Inflammation Regulation

A growing body of evidence shows that acupuncture can regulate inflammation by influencing monocytes and macrophages—key immune cells involved in both protective responses and chronic inflammatory disease. Recent studies highlight several mechanisms through which acupuncture may help rebalance the immune system and support gastrointestinal and liver health.

1. Suppressing M1 Macrophages and Protecting the Intestinal Barrier

Acupuncture has been shown to inhibit M1-type macrophage activation by suppressing the TLR4/MyD88 inflammatory pathway and reducing harmful microbial and inflammatory substances released in the intestinal tract. This helps maintain intestinal barrier integrity and alleviates inflammatory bowel disease (IBD).

• Electroacupuncture (EA) at ST36 reduces M1-type macrophages and promotes M2-type macrophages by inhibiting the TLR4/MyD88 pathway.
• This down-regulates NLRP3/IL-1β in colonic macrophages and lowers inflammatory factors such as IL-6, IL-12, IL-17, TNF-α, CRP, IFN-γ in the colon and serum.
• At the same time, EA up-regulates anti-inflammatory substances such as IL-10, reduces white blood cell infiltration, supports repair of the intestinal mucosa, and slows IBD-related weight loss.
• EA also increases adiponectin secreted from mesenteric adipose tissue, further inhibiting macrophage infiltration and pro-inflammatory cytokine release.

2. Improving Postoperative Ileus via Macrophage Modulation

Manual acupuncture (MA) at ST36, SP6, and LR3 inhibits NF-κB activation in M1 macrophages. By suppressing the IL-6/miR-19a/KIT axis, this approach helps restore the function of interstitial Cajal cells (ICCs), the pacemaker cells of gastrointestinal motility, and effectively improves inflammation in postoperative ileus.

3. Reducing Visceral Hypersensitivity in IBD

EA at ST25 and ST36 reduces the amount of macrophage-secreted IL-18 in the colon, which helps relieve visceral hypersensitivity in post-inflammatory IBD models.

4. Regulating Liver Macrophages in Fatty Liver and Steatohepatitis

In high-fat diet-induced non-alcoholic steatohepatitis (NASH), macrophage activation mediated by the TLR4/MyD88 pathway plays an important role in liver injury. Acupuncture appears to modulate this process:

• MA at ST36, CV4, and KI1 inhibits recruitment and activation of hepatic macrophages via the TLR4/MyD88 and NF-κB pathways and down-regulates IL-1β and TNF-α, thereby improving related symptoms.
• EA at ST40, SP9, and SP6 enhances the expression of Sirt1, a representative histone deacetylase (HDAC), strongly inhibiting the NLRP3/NF-κB pathway.
• This reduces downstream inflammatory cytokines such as IL-1β, IL-6, TNF-α and improves liver-related markers including ALT, AST, TG, and TC, benefiting non-alcoholic fatty liver disease (NAFLD) models.

5. Reducing Oxidative Stress Through Macrophage-Related Pathways

Macrophages stimulate oxygen-dependent killing pathways after phagocytosing pathogens, a process that consumes large amounts of oxygen and is closely linked to oxidative stress. Acupuncture helps regulate this aspect of inflammation:

• EA at ST36 inhibits HO-1 and its key transcription factor Nrf2, thereby suppressing oxidative stress while promoting a positive feedback loop of anti-inflammatory factors such as IL-10 in ulcerative colitis models.
• MA at ST36, CV4, and KI1 significantly reduces 8-OHdG-positive cells and MDA levels, lowers liver free fatty acids, and inhibits reactive oxygen species (ROS) formation, improving oxidative stress, necrotizing inflammation, and fibrosis in NAFLD models.
• Acupuncture can also alleviate morphine- and acetaminophen-induced hepatotoxicity by supporting antioxidant defense systems.

6. Beyond Macrophages: Mast Cells and Digestive Inflammation

Beyond macrophages, acupuncture also alleviates inflammatory diseases in the digestive system by regulating mast cells. In irritable bowel syndrome (IBS) and TNBS-induced colitis models, EA at ST36 reduces the number of mast cells, down-regulates TLR4, IL-1β, and IL-8 released by mast cells in colonic tissues, and improves visceral hypersensitivity.

越來越多研究顯示，針灸能透過調節單核細胞與巨噬細胞這類關鍵免疫細胞， 來影響全身發炎反應。這些實驗結果特別與腸道發炎（如 IBD）以及脂肪肝、 脂肪性肝炎等疾病有關，提供針灸介入「腸–肝–免疫軸」的機制線索。

一、抑制 M1 型巨噬細胞、保護腸道黏膜與腸道屏障

多項研究指出，針灸可抑制 TLR4/MyD88 發炎訊號路徑，以及降低 巨噬細胞與腸道微生物所釋放的發炎物質，從而維持腸道上皮屏障完整，減輕 發炎性腸病（IBD）相關症狀。

• 電針足三里（ST36） 能降低 M1 型巨噬細胞比例，並上調 M2 型 巨噬細胞，與抑制 TLR4/MyD88 路徑有關。
• 進一步下調結腸巨噬細胞中的 NLRP3/IL-1β，同時降低 IL-6、IL-12、IL-17、TNF-α、C 反應蛋白（CRP）、IFN-γ 等多種促發炎 因子在結腸與血清中的表現。
• 電針亦可上調抗發炎細胞激素 IL-10，減少白血球浸潤，促進腸黏膜 修復，並延緩結腸炎造成的持續體重下降。
• 此外，電針能提升腸系膜脂肪組織分泌的 脂聯素（adiponectin）， 進一步抑制巨噬細胞浸潤與促發炎細胞激素釋放。

二、改善術後腸麻痺（POI）：恢復腸道起搏細胞功能

在術後腸麻痺模型中，手針 足三里（ST36）、三陰交（SP6）、太衝（LR3） 能抑制 M1 型巨噬細胞中的 NF-κB 活化，透過抑制 IL-6/miR-19a/KIT 軸，恢復腸道間質卡氏細胞（ICCs，腸道蠕動的 節律起搏細胞）功能，從而改善 POI 相關發炎與腸蠕動障礙。

三、降低 IBD 相關的內臟高敏感

電針 天樞（ST25） 與 足三里（ST36） 能降低結腸 巨噬細胞分泌的 IL-18，對於發炎後的腸道內臟高敏感症狀具有 緩解作用，對 IBD 的疼痛與不適改善尤為重要。

四、調節肝臟巨噬細胞：脂肪肝與非酒精性脂肪性肝炎

在高脂飲食誘發的非酒精性脂肪性肝炎（NASH）模型中，經由 TLR4/MyD88 活化的肝臟巨噬細胞是造成肝臟發炎與損傷的重要因素。 針灸對此展現出調節潛力：

• 手針 足三里（ST36）、關元（CV4）、湧泉（KI1） 可抑制肝臟巨噬 細胞的募集與活化，透過下調 TLR4/MyD88 與 NF-κB 路徑及其下游的 IL-1β、TNF-α，改善脂肪性肝炎相關症狀。
• 在非酒精性脂肪肝（NAFLD）模型中，電針 豐隆（ST40）、陰陵泉（SP9）、三陰交（SP6） 能明顯上調去乙醯化酶 Sirt1 的表現，進而抑制 NLRP3/NF-κB 發炎訊號路徑。
• 這樣的調節可降低 IL-1β、IL-6、TNF-α 等發炎細胞激素， 並改善 ALT、AST、三酸甘油脂（TG）、總膽固醇（TC） 等肝臟代謝與功能指標。

五、調控氧化壓力：從巨噬細胞到自由基

巨噬細胞在吞噬病原體後，會啟動高度耗氧的殺菌過程，與 氧化壓力和自由基產生密切相關。研究指出，針灸在這部分也具調節作用：

• 電針 足三里（ST36） 能抑制 血基質氧合酶-1（HO-1） 與其關鍵轉錄因子 Nrf2 的表現，減少氧化壓力，同時促進 IL-10 等抗發炎因子的正回饋調節，改善潰瘍性結腸炎（UC） 相關症狀。
• 手針 足三里（ST36）、關元（CV4）、湧泉（KI1） 可顯著降低 8-OHdG 陽性細胞與 MDA 濃度，減少肝臟自由脂肪 酸與活性氧（ROS）的產生，改善 NAFLD 模型中的氧化壓力、壞死性發炎與 纖維化。
• 其他研究亦指出，針灸可透過強化抗氧化防禦系統，減輕嗎啡與乙醯胺酚 所造成的肝毒性。

六、不只巨噬細胞：針灸對肥大細胞與腸道發炎的調節

除了巨噬細胞外，針灸也能透過調節肥大細胞改善腸道相關發炎疾病。 在腸躁症（IBS）與 TNBS 誘導結腸炎模型中，電針 足三里（ST36） 能降低結腸組織中的肥大細胞數量， 並下調其釋放的 TLR4、IL-1β、IL-8，進一步改善腸道內臟高敏感 與腹痛症狀。