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Clinical Research


Acupoint-catgut embedment combined with medication does not decrease interleukin-6 levels serum in patients with gastroesophageal reflux disease: a randomized controlled clinical trial

Andalia Fitri,¹ Murdani Abdullah,¹ Iris Rengganis,¹ Hasan Mihardja,² Intan Suri Baginda,² Ainil Masthura²



pISSN: 0853-1773 • eISSN: 2252-8083

https://doi.org/10.13181/mji.v28i3.1850 Med J Indones. 2019;28:241–5


Received: February 8, 2017

Accepted: May 13, 2019


Authors' affiliation:

¹Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia,

²Department of Medical Acupuncture, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia


Corresponding author:

Murdani Abdullah

Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital,

Jalan Diponegoro No. 71, Kenari, Senen, Central Jakarta 10310, DKI Jakarta, Indonesia

Telp/Fax: +62-21-3153957

E-mail: murdani08@gmail.com




Gastroesophageal reflux disease (GERD) is a pathological condition caused by the reflux of stomach contents into the esophagus. GERD is a multifactorial disorder with an increase in prevalence worldwide. Interleukin-6 (IL-6) is a proinflammatory cytokine that is commonly found in the esophageal mucosa of GERD patients and associated with esophageal motor disorders. Acupoint-catgut embedment has long been known as adjunctive therapy for GERD. This study was aimed to establish the effect of acupoint-catgut embedment combined with medication on the IL-6 serum levels of patients with GERD.



This single-blind randomized controlled trial involved 40 GERD patients from the Gastroenterology Outpatient Clinic of Cipto Mangunkusumo Hospital that were randomly allocated to either catgut-embedding therapy plus medication or sham acupuncture with medication. Catgut-embedding therapy was given two times at CV12 (Zhongwan), ST36 (Zusanli), and BL21 (Weishu) every 15 days. Serum levels of IL-6 were measured by enzyme-linked immunosorbent assay as research output.



There were no significant differences in the baseline levels of proinflammatory (IL-6) mediators between the groups. After 1-month treatment, the median levels of IL-6 were statistically insignificant decreased in catgut-embedding therapy plus medication versus sham acupuncture with medication (0.15 versus -0.16 pg/ml, respectively; p = 0.14).



The results suggest that catgut-embedding therapy has not been proven to statistically influence the levels of IL-6 in patients with GERD.



acupuncture therapy, GERD, interleukin-6



Gastroesophageal reflux disease (GERD) is a pathological state caused by the reflux of stomach contents into the esophagus that results in a variety of troublesome symptoms in the esophagus and extra esophagus.¹ GERD can lower health-related quality of life, and its prevalence is increasing worldwide.1,2 The prevalence of GERD in Asia is lower than in Western countries, although some Asian countries have shown an increasing trend.³ Data from Cipto Mangunkusumo Hospital indicate the increasing prevalence of esophagitis, from 5.7% in 1997 to 25.18% in 2002.⁴ Pathological reflux is more dominant than the ability of the antireflux barrier esophagus, causing injury to the esophageal squamous epithelium tissue. Interleukin-6 (IL-6) is a proinflammatory cytokine that is commonly found in the esophageal mucosa of patients with GERD and is associated with motor disorders of the esophageal muscle.5,6 IL-6 also naturally occurs in a soluble form, which can be found in serum.7

Acupuncture is now considered by medical practitioners as one of the nonpharmacological treatments of GERD. Some randomized controlled clinical trials have proven the effectiveness of acupuncture therapy for GERD, especially against the symptoms of heartburn, acid reflux, and bile salts, as well as esophageal mucosal damage.8–10 Stimulation of acupuncture points on the peripheral nervous system causes binding between catecholamines and β2 receptor on immune cells, resulting in decreased levels of proinflammatory cytokines IL-6.¹¹ Acupoint-catgut embedment is one of acupuncture method that involves catgut implantation at acupoints, with advantages of using fewer acupoints, less frequent therapy, and prolonged excitatory effects.¹²

Research on the mechanisms of how acupuncture work on proinflammatory and antiinflammatory cytokines is limited. Hence, the aim of this study was to establish the effect of acupointcatgut embedment combined with medication on the IL-6 serum levels of patients with GERD.




This study was a single-blind randomized clinical trial that was conducted at the Gastroenterology Clinic of Internal Medicine, Cipto Mangunkusumo Hospital, in August 2016 (Figure 1). This research was a collaboration between the Division of Gastroenterology, Department of Internal Medicine, and the Department of Medical Acupuncture. The inclusion criteria of this study were men and women aged between 18 and 59 years with a GERD questionnaire (GERDQ) score ≥8. The exclusion criteria were alarming signs such as anemia, gastrointestinal bleeding, progressive dysphagia, weight loss without definite cause, and abdominal masses, and contraindications of acupointcatgut embedment including medical emergency, pregnancy, malignancy, blood clotting disorders, anticoagulant medication consumption, animal protein allergy history, diabetes mellitus with blood sugar levels >200 mg/dl, and previous acupointcatgut embedment history. Calculation of the sample was based on as follows: α = 5%, β = 20%, and S = 9.82; thus, 40 research subjects were obtained. Random allocation of samples was done using a computerbased program. Concealment technique was used to avoid procedure selection bias.


Figure 1. Diagram of subject recruitment. GERD=gastroesophageal reflux disease; GERDQ=GERD questionnaire; IL-6=interleukin-6


Patients who met the inclusion criteria were allocated randomly into either the catgut-embedding group plus medication or the sham acupuncture group plus medication, and then, as much as 5 cc of venous blood sample was drawn. On day 1, acupoint-catgut embedment at CV12 (Zhongwan), ST36 (Zusanli), and BL21 (Weishu) was done (Figure 2). Then, the same procedure was repeated at these points on the 15th day. The process in the sham acupuncture group is almost the same as the catgut-embedding group, only that the latter touches the skin surface at a predetermined point. On the 30th day, as much as 5 cc of venous blood sample was drawn again. IL-6 was examined at the Laboratory of Research and Esoteric Prodia using the Human IL-6 Quantikine® HS enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems Inc., Minneapolis, USA), which employs the quantitative sandwich enzyme immunoassay technique. This is a special kit intended for this research.


Figure 2. Acupuncture points. (a) CV12 (Zhongwan); (b) BL21 (Weishu); (c) ST36 (Zusanli)


Data were analyzed using the SPSS software, version 23 (IBM). The Mann–Whitney U test was performed for the inter-group analysis and Wilcoxon signed-rank test for intra-group analysis.

This research has been approved by the Health Research Ethics Committee of the Faculty of Medicine, Cipto Mangunkusumo Hospital, through letter no. 688/UN2.F1/ETHICS/2016. The subjects involved in the study have agreed to participate by signing an informed consent of confidentiality and voluntary noncoercion.




This study was conducted on 40 patients with GERD who met the inclusion and exclusion criteria. The characteristics of the research subjects are listed in Table 1.


Table 1. Characteristics of the subject


Comparison of the median difference in the levels of IL-6 in the catgut-embedding therapy and sham acupuncture groups was not statistically significant (p = 0.14; Table 2). There was no difference of IL-6 between pre- and post-catgut-embedding therapy (p = 0.59).


Table 2. Comparison of median difference in the levels of IL-6





This was the first study in Indonesia that uses acupoint-catgut embedment in GERD patients to evaluate the changes of IL-6 serum levels. The result showed that there was a decrease in the levels of IL-6 in patients with GERD after catgut-embedding therapy plus medication, but the decline is small and it did not show significant differences. Median changes of IL-6 were 0.15 in the catgut-embedding therapy group and -0.16 in the sham acupuncture group. There was no difference of IL-6 in the catgutembedding therapy and sham acupuncture (p = 0.14).

Study on acupuncture in GERD is very limited. However, previous studies, including Dickman et al,⁸ Zhang et al,⁹ Zhang et al,¹³ and Baginda et al,¹⁴ have shown that acupuncture therapy was better at lowering symptom scores and improving quality of life in patients with GERD.¹⁴

The medications used for comparison in this study were mostly PPI, which is the standard therapy for patients with GERD. PPIs have antiinflammatory effects by inhibiting the production of proinflammatory cytokines. Giving lansoprazole can reduce proinflammatory cytokines including IL-6, IL-8, and tumor necrosis factor-α (TNF-α). The mechanism of how PPI can reduce the production of proinflammatory cytokines in the epithelial and endothelial cells is still not clear.¹⁵ A study by Hashioka et al¹⁶ about the anti-inflammatory effects of PPIs (lansoprazole and omeprazole) in the microglial cells has shown that both PPIs significantly reduced the levels of TNF-α and IL-6. This suggests that PPI has anti-inflammatory effects and can lower neurotoxicity in human microglial cells.¹⁶

In this study, the IL-6 level showed a reduction after the intervention in both the treatment and control groups. However, these results were statistically insignificant. This can be due to participants in each group were still taking PPI during research so the inflammatory mediators can decrease despite the intervention of acupoint-catgut embedment therapy.

IL-6 is a pleiotropic cytokine that has broad biological activity in the regulation of the immune system, hematopoiesis, inflammation, and oncogenesis.¹⁷ Various diseases caused by chronic inflammation such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis, colitis, and obesity can contribute to increased levels of IL-6. The exclusion criteria in this study did not remove other inflammatory diseases, as this may cause an insignificant decrease in IL-6 levels. Therefore, we had to be strict on selecting the subjects to obtain better research results.

IL-6, although largely a proinflammatory cytokine, can also act as anti-inflammatory cytokines.7,17–19 In this study, the decreased levels of IL-6 were not significant. This might happen because of synergism between the anti-inflammatory effects of acupuncture and the role of IL-6 as anti-inflammatory cytokines instead of proinflammatory cytokines, which were considered as the pathophysiology of GERD.

Various studies suggest that stimulating acupuncture points on the peripheral adrenal axis could activate neuroendocrine, which could result in increased catecholamines. The bond between catecholamines and β2 adrenergic receptors on immune cells triggers a decline in the levels of proinflammatory cytokines IL-6.¹⁹ These results have been inconsistent with the theory of acupoint-catgut embedment therapy as there are insignificantly reduced levels of IL-6.

The limitations of this study include the consumption and lack of intake schedule of PPI that had an anti-inflammatory effect on the study subjects and the absence of other chronic disease exclusion in the study subjects that can reduce IL-6 levels without acupuncture, even though this has been anticipated by doing randomization. However, if the exclusion criteria are very strict, then it will be difficult to extrapolate the research results into the community. In addition, a short study time of only 1 month and catgut-embedding therapy done only two times is not standard therapy. There is also no other outcome assessment such as decreased drug requirements, clinical assessment with GERDQ, anatomical assessment, and quality of life evaluation.

In conclusion, this study suggests that catgutembedding therapy has not been statistically proven to influence the levels of IL-6 in patients with GERD (p > 0.05). Catgut-embedding therapy can still be used as adjunctive therapy in addition to regular PPI therapy as it provides some reduction in IL-6 levels.



Conflict of Interest

The authors affirm no conflict of interest in this study.



Dr. Murdani Abdullah is a recipient of the Grant “Publikasi Internasional Terindeks Tugas Akhir Mahasiswa Universitas Indonesia.


Funding Sources

This study was funded by “Publikasi Internasional Terindeks Tugas Akhir Mahasiswa Universitas Indonesia” grant.





  1. Dinamithra NP, Nawarathne NM. Diagnosis and management of gastro-oesophageal reflux disease. The Sri Lanka Journal of Surgery. 2015;33(1):14–9.
  2. Tack J, Becher A, Mulligan C, Johnson DA. Systematic review: the burden of disruptive gastro-oesophageal reflux disease on health-related quality of life. Aliment Pharmacol Ther. 2012;35(11):1257–66.
  3. Leow AH, Lim YY, Liew WC, Goh KL. Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population–20-year experience over three time periods. Aliment Pharmacol Ther. 2016;43(7):1–7.
  4. Indonesian Society of Gastroenterology. National consensus on the management of gastroesophageal reflux disease in Indonesia. Acta Med Indones. 2014;46(3):263–71.
  5. Rieder F, Biancani P, Harnett K, Yerian L, Falk GW. Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis. Am J Physiol Gastrointest Liver Physiol. 2010;298(5):G571–81.
  6. Altomare A, Guarino MP, Cocca S, Emerenziani S, Cicala M. Gastroesophageal reflux disease: update on inflammation and symptom perception. World J Gastroenterol. 2013;19(39):6523–8.
  7. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The proand anti-inflammatory properties of cytokine interleukin-6. Biochim Biophys Acta. 2011;1813(5):878–88.
  8. Dickman R, Schiff E, Holland A, Wright C, Sarela SR, Han B, et al. Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose and refractory heartburn. Aliment Pharmacol Ther. 2007;26(10):1333–44.
  9. Zhang CX, Qing YM, Guo BR. Clinical study on treatment of gastroesophageal reflux by acupuncture. Chin J Integr Medicine. 2010;16(4):298–303.
  10. Yin J, Chen JD. Gastrointestinal motility disorders and acupuncture. Auton Neurosci. 2010;157(1–2):31–7.
  11. Kavoussi B, Ross BE. The neuroimmune basis of antiinflammatory acupuncture. Integr Cancer Ther. 2007;6(3):251–7.
  12. Kang SG, Zhang ML, Duan XD, Zhang XP, Zhang X, Xu XK, et al. Exploration to the disease spectrum of acupoint catgut-embedding therapy. World J Acupunct Moxibustion. 2012;22(1):53–8.
  13. Zhang C, Guo L, Guo X, Guo X, Li G. Clinical curative effect of electroacupuncture combined with zhizhukuanzhong capsules for treating gastroesophageal reflux disease. J Tradit Chin Med. 2012;32(3):364–71.
  14. Baginda IS, Srilestari A, Abdurrohim K, Abdullah M. Pengaruh terapi kombinasi akupunktur tanam benang dan medikamentosa terhadap gejala dan kualitas hidup penderita gastroesophageal reflux disease [thesis]. Jakarta (Indonesia): Universitas Indonesia; 2016. Indonesian.
  15. Ismail LA, Ibrahim AA, Abdel-Latif GA, El-Haleem DA, Helmy G, Labib LM, et al. Effect of acupuncture on body weight reduction and inflammatory mediators in Egyptian obese patients. Open Access Maced J Med Sci. 2015;3(1):85–90.
  16. Savarino V, Di Mario F, Scarpignato C. Proton pump inhibitors in GERD: an overview of their pharmacology, efficacy and safety. Pharmacol Res. 2009;59(3):135–53.
  17. Ghebremariam YT, LePendu P, Lee JC, Erlanson DA, Slaviero A, Shah NH, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845–53.
  18. Kedika RR, Souza RF, Spechler SJ. Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications. Dig Dis Sci. 2009;54(11):2312–7.
  19. Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci. 2012;8(9):1237–47.