Acupuncture, Lymphocytes, and Inflammation in Respiratory Diseases

Lymphocytes are key decision-makers in how the immune system reacts to inflammation, especially in the lungs. When T helper (Th) cells and other lymphocyte subsets become imbalanced, they can drive the development and persistence of many respiratory diseases, including allergy, asthma, and chronic airway inflammation. Recent research suggests that acupuncture can gently rebalance these immune cells and reduce inflammation through specific acupoints and signaling pathways.

This article summarizes how acupuncture influences Th cells, innate lymphoid cells (ILCs), and key cytokines to protect lung function.

1. Th Cell Imbalance in Respiratory Inflammation

In the respiratory system, excessive Th2-dominant responses are closely associated with allergy and asthma. Th2 cells secrete cytokines such as IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, IL-25, and IL-31, which:

• Activate eosinophils.
• Promote B cell proliferation and antibody production.
• Generate exaggerated immune responses to otherwise harmless allergens.

When Th2 and Th17 responses dominate over Th1 and regulatory T cells (Treg), the result is persistent airway inflammation, mucus hypersecretion, and airway hyperresponsiveness. Acupuncture appears to help by shifting this imbalance.

2. Balancing Th1/Th2/Th17/Treg in Asthma with GV14, BL12, and BL13

Manual acupuncture (MA) at GV14 (Dazhui), BL12 (Fengmen), and BL13 (Feishu) in asthma models can:

• Up-regulate Th1 cytokines such as IL-2 and IL-12.
• Increase Treg markers like Foxp3 and the regulatory cytokine IL-10.
• Down-regulate Th2 cytokines including IL-4, IL-5, IL-13.
• Reduce Th17 cytokines, especially IL-17A.

This shifts the immune state from a Th2/Th17-dominant profile toward a more balanced Th1/Treg-dominant pattern, thereby easing allergic airway inflammation.

Mechanistically, IFN-γ released by Th1 cells inhibits Th2 differentiation and function, while IL-4 from Th2 cells suppresses Th1. In addition, IL-2 produced by Th1 cells binds to IL-2 receptors on activated T cells, promoting T cell proliferation via autocrine and paracrine effects. Acupuncture amplifies these regulatory loops to calm allergic asthma.

3. ST36, BL13, LI20, and LI4 in Sinusitis

In sinusitis models, electroacupuncture (EA) at ST36 (Zusanli), BL13 (Feishu), LI20 (Yingxiang), and LI4 (Hegu):

• Increases IFN-γ and IL-10.
• Promotes differentiation of Th1 and Treg cells.
• Produces an overall anti-inflammatory effect in the sinonasal mucosa.

These immunological changes are accompanied by reduced inflammatory cell infiltration in the sinus submucosa and gradual repair of damaged pseudo-stratified epithelial cells.

4. The IL-33/ST2 Pathway and Th Cell Regulation

Acupuncture also regulates Th cells through the IL-33/ST2 pathway. Stimulation at GV14, BL12, and BL13:

• Inhibits binding of IL-33 to its membrane receptor ST2L.
• Up-regulates soluble ST2 (sST2), which acts as a decoy receptor.
• Down-regulates TNF-α, IL-1β, and IL-33.
• Further up-regulates Treg cytokines and down-regulates Th17 cytokines.

These effects effectively protect lung function, reduce airway inflammation, and decrease mucus secretion in asthma models.

5. Acupuncture and Innate Lymphoid Cells (ILCs)

Innate lymphoid cells (ILCs) are a newly identified subset of lymphocytes that lack adaptive antigen receptors and are distinct from T and B cells. They are mainly distributed in mucosal barrier tissues and include ILC1, ILC2, ILC3, NK cells, and LTi cells.

Among them, ILC2 cells release Th2-type cytokines and regulate inflammatory responses, tissue homeostasis, and mucosal repair in respiratory diseases. However, excessive ILC2 activation contributes to airway inflammation.

MA at GV14, BL12, and BL13 in asthmatic mice has been shown to:

• Inhibit ILC2 influx into the lungs.
• Reduce IL-5, IL-9, and IL-13 levels in bronchoalveolar lavage fluid.
• Up-regulate sST2, leading to down-regulation of IL-33 and IL-25.

This helps protect the respiratory epithelium from ovalbumin-induced injury and significantly alleviates airway inflammation and mucus secretion.

6. Acupoint Selection and Multi-Point Combinations

Across different inflammatory respiratory disease models, several acupoints appear repeatedly:

• BL13 (Feishu)
• ST36 (Zusanli)
• LI4 (Hegu)

Sham acupuncture often uses GB30 (Huantiao) or non-acupoints located about 5 mm beside the real acupoint. The combinations BL13 + ST36 + GV14 and BL12 + BL13 are among the most common and effective.

Importantly, multi-point combinations frequently outperform single acupoints. For example, EA at BL13 combined with ST36 in asthma models:

• Reduces inflammatory cell aggregation.
• Down-regulates pro-inflammatory cytokines TNF-α and IL-1β.
• Decreases epithelial smooth muscle thickness and goblet cell metaplasia.
• Improves bronchiole structure.

In contrast, BL13 alone shows no significant effect in the same model.

7. Synergy Between Acupuncture and Medication

Some studies report a synergistic effect when acupuncture is combined with medication. For instance, combined treatment with EA and virus-encoded IL-10 enhances the therapeutic effect on sinusitis by specifically targeting IFN-γ.

Based on the traditional theory of meridian–viscera correlation, some researchers speculate that acupuncture may help guide drugs to target organs. However, the laws and mechanisms underlying this synergy remain to be clarified.

8. Integrated View: Innate & Adaptive Immunity

Overall, studies suggest that acupuncture exerts strong anti-inflammatory effects in the respiratory system through both innate and adaptive immunity:

• Inhibiting activation of innate immune cells such as monocytes/macrophages and ILCs via pattern recognition receptors like TLR4.
• Promoting PPARγ expression and suppressing NF-κB and MAPK pathways.
• Modulating the expression and acetylation of HDAC2 in the nucleus.
• Inhibiting NLRP3 inflammasome formation via the ROS/Nrf2 pathway.
• Down-regulating pro-inflammatory factors such as TNF-α, IL-1β, IL-6, IL-5, IL-9, IL-13, IL-18.
• Up-regulating anti-inflammatory or regulatory factors such as IL-10, IL-25, and IL-33 (in a context-dependent manner).
• Correcting Th1/Th2/Th17/Treg imbalance, reducing airway inflammation, pulmonary fibrosis, and interstitial edema.

Through these multi-layered mechanisms, acupuncture shows therapeutic potential for both acute and chronic respiratory diseases.

淋巴細胞是免疫系統的關鍵決策者，特別是在肺與呼吸道發炎中。當 T 輔助細胞 （Th 細胞）等淋巴細胞亞群失衡時，會推動多種呼吸道疾病的形成與惡化，包括 過敏、氣喘與慢性氣道發炎。近年研究顯示，針灸可以透過調整 Th 細胞、先天淋 巴樣細胞（ILCs）與多種細胞激素，達到減輕發炎、保護肺功能的效果。

下文整理了該文獻中關於「淋巴細胞與針灸」的重點機制與穴位組合。

一、Th 細胞失衡如何造成呼吸道發炎？

在呼吸系統中，Th2 反應過強是過敏與氣喘的重要基礎。Th2 細胞會 分泌 IL-3、IL-4、IL-5、IL-6、IL-10、IL-13、IL-25、IL-31 等細胞激素：

• 活化嗜酸性球。
• 促進 B 細胞增生與抗體產生。
• 對無害過敏原產生過度免疫反應，導致氣道過敏與慢性發炎。

當 Th2、Th17 佔上風，而 Th1、Treg 相對不足時，氣道 就容易出現持續性的發炎、黏液分泌增加與氣道高反應。針灸的作用之一，就是協 助把這個失衡重新拉回來。

二、大椎（GV14）＋風門（BL12）＋肺俞（BL13）：重新平衡 Th1／Th2／Th17／Treg

在氣喘動物模型中，針刺 大椎（GV14）、風門（BL12）、肺俞（BL13） 可：

• 上調 Th1 細胞激素：如 IL-2、IL-12。
• 提升調節型 T 細胞標誌 Foxp3 以及調節性細胞激素 IL-10。
• 下調 Th2 細胞激素：如 IL-4、IL-5、IL-13。
• 減少 Th17 相關細胞激素，特別是 IL-17A。

結果是將氣喘模型由原本的 Th2／Th17 優勢，轉為較為平衡的 Th1／Treg 優勢，氣道發炎因此明顯減輕。

在這個過程中，Th1 分泌的 IFN-γ 會抑制 Th2 分化與功能，而 Th2 釋放的 IL-4 又會反向抑制 Th1。Th1 釋放的 IL-2 則與活化 T 細胞表 面的 IL-2 受體結合，透過自分泌與旁分泌進一步促進 T 細胞增殖。針灸透過強化這 些交互調控，來舒緩過敏性氣道發炎。

三、足三里（ST36）＋肺俞（BL13）＋迎香（LI20）＋合谷（LI4）：改善鼻竇炎

在鼻竇炎模型中，電針 足三里（ST36）、肺俞（BL13）、迎香（LI20）、 合谷（LI4） 能：

• 提高 IFN-γ 與 IL-10 濃度。
• 促進 Th1 與 Treg 細胞分化。
• 產生整體性的抗發炎效果，減輕鼻竇黏膜發炎。

在組織層面上，這些變化伴隨鼻竇黏膜下發炎細胞浸潤減少，以及受損假複層上皮 的修復，顯示針灸不僅調節免疫，也協助黏膜結構恢復。

四、IL-33／ST2 訊號軸與 Th 細胞平衡

針灸也透過 IL-33／ST2 訊號通路影響 Th 細胞平衡。針刺 GV14、BL12、BL13 可：

• 抑制 IL-33 與其膜上受體 ST2L 的結合。
• 上調 可溶性 ST2（sST2），如同「誘餌受體」中和 IL-33。
• 降低 TNF-α、IL-1β、IL-33 濃度。
• 同時上調 Treg 相關細胞激素並下調 Th17 相關細胞激素。

整體而言，這些變化可以保護小鼠的肺功能，減輕氣道發炎與黏液分泌。

五、先天淋巴樣細胞（ILCs）與 ILC2：針灸的抑制作用

除了經典的 T 細胞之外，針灸也會影響 先天淋巴樣細胞（ILCs）。ILCs 是一群 沒有特異性抗原受體的淋巴細胞，與 T、B 細胞不同，主要分布在黏膜屏障組織， 包括 ILC1、ILC2、ILC3、NK 細胞與 LTi 細胞 等。

其中 ILC2 特別與呼吸道發炎密切相關。ILC2 會釋放 Th2 型細胞激素，調 節組織穩態與黏膜修復，但過度活化時會推動過敏與氣喘。

在氣喘小鼠模型中，針刺 GV14、BL12、BL13 可：

• 抑制 ILC2 進入肺組織。
• 降低肺泡灌洗液中的 IL-5、IL-9、IL-13。
• 上調 sST2，進一步降低 IL-33、IL-25。

這些變化能保護呼吸道上皮免於卵清蛋白誘導的損傷，大幅減少氣道發炎與黏液 分泌。

六、穴位選擇與組合：多穴位方案的優勢

在各種呼吸道發炎模型中，經常出現的核心穴位包括：

• 肺俞（BL13）
• 足三里（ST36）
• 合谷（LI4）

對照組常使用的假針灸點包括 環跳（GB30），或距離真正穴位約 5 mm 的非穴位 點。常見且有效的配穴模式有 BL13 ＋ ST36 ＋ GV14 以及 BL12 ＋ BL13。

多項研究顯示，多穴位組合 通常優於單一穴位。以氣喘模型為例，電針 BL13 ＋ ST36 可：

• 減少發炎細胞聚集。
• 下調 TNF-α、IL-1β。
• 降低上皮和平滑肌厚度與杯狀細胞化生。
• 改善細支氣管結構。

相較之下，單刺 BL13 在同一模型中則未顯示顯著療效。

七、針藥合用的協同效果

部分研究指出，當針灸與藥物合併使用時，可能產生協同效應。例如，電針合併 病毒載體 IL-10 治療鼻竇炎，可透過特異性調節 IFN-γ 增強療效。

有學者以「經絡–臟腑相關」理論推測，針灸可能具有「引藥歸經」或幫助藥物更 精準作用於標的臟腑的效果。不過，目前針藥協同的具體規律與機制仍需更多實證 研究釐清。

八、整體觀點：先天＋後天免疫，針灸同時介入

綜合上述研究，針灸在呼吸系統中的抗發炎機制，橫跨 先天免疫 與 適應性免疫 兩大層面：

• 抑制單核球／巨噬細胞與 ILCs 等先天免疫細胞的過度活化，透過 TLR4 等模式識別受體調節 PPARγ、NF-κB、MAPK。
• 影響核內 HDAC2 的表現與乙醯化狀態，參與慢性氣道發炎調控。
• 透過 ROS/Nrf2 路徑抑制 NLRP3 發炎小體 合成。
• 下調 TNF-α、IL-1β、IL-6、IL-5、IL-9、IL-13、IL-18 等促發炎細胞激素。
• 上調 IL-10、IL-25、IL-33 等具調節作用的細胞激素（視情境而定）。
• 修正 Th1／Th2／Th17／Treg 失衡，減少氣道發炎、肺纖維化與間質水腫。

透過這些多層次作用，針灸對急性與慢性呼吸道疾病（如氣喘、鼻竇炎、COPD、 急性肺損傷等）都展現了潛在的治療價值與科學依據。