Effect of ginger-partitioned moxibustion on immunocytokines in patients with chronic nonbacterial prostatitis

Li Guo-dong (李國棟), Li Shu-yi (李樹義)

1 Maternity and Child Care Centers in Lunan District, Tangshan City, Hebei 063000, China

2 The Ninth Hospital of Tangshan, Hebei 063000, China

Effect of ginger-partitioned moxibustion on immunocytokines in patients with chronic nonbacterial prostatitis

Li Guo-dong (李國棟)1, Li Shu-yi (李樹義)2

1 Maternity and Child Care Centers in Lunan District, Tangshan City, Hebei 063000, China

2 The Ninth Hospital of Tangshan, Hebei 063000, China

Objective:To observe the effect of ginger-partitioned moxibustion on immunocytokines in patients with chronic nonbacterial prostatitis (CNP).

Methods:A total of 80 CNP patients were randomly allocated into two groups according to their visiting sequence, 40 cases in each group. Cases in the observation group were treated with oral Tamsulosin Hydrochloride Sustained Release Capsules (Harnal) (0.2 mg for each dose, one dose a day) and ginger-partitioned moxibustion at Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3) and bilateral Zusanli (ST 36), Sanyinjiao (SP 6), Pangguangshu (BL 28), Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34) (once a day). Cases in the control group were treated with the oral Western medication alone (same administration as those in the observation group). Cases in both groups were treated for 28 d. Before and after treatment, the CD3+, CD4+, CD8+, CD4+CD25+, CD4+CD25+Foxp3+, transforming growth factor (TGF )-β1, immunoglobulin (Ig) A, IgE, IgG and IgM were detected and scored using National Institutes of Health chronic prostatitis symptom index (NIH-CPSI).

Results:The total effective rate was 90.0% in the observation group, versus 72.5% in the control group, showing a statistical difference (P＜0.05). After treatment, the CD3+, CD4+, CD8+, CD4+CD25+, CD4+CD25+Foxp3+, TGF-β1, IgA, IgG and IgM were significantly increased in both groups, showing statistical differences (P＜0.05). There were between-group statistical differences in CD3+, CD4+, CD8+, CD4+CD25+, CD4+CD25+Foxp3+, TGF-β1, IgA, IgG, IgE, IgM, total NIH-CPSI score and pain and discomfort score (P＜0.05).

Conclusion:Ginger-partitioned moxibustion can improve clinical symptoms of CNP patients by improving their immune function.

Prostatitis; Moxibustion Therapy; Indirect Moxibustion; Ginger-partitioned Moxibustion; Immunity

Chronic nonbacterial prostatitis (CNP) is a major type of chronic prostatitis. It’s mainly characterized by pain, urgency and frequency of urination, coupled with soreness, pain and discomfort in the lower back and abdomen. These symptoms can affect the patient’s quality of life. Chinese medicine, especially acupuncture can help alleviate some CNP symptoms. To explore the action mechanism of ginger-partitioned moxibustion on CNP, we’ve observed changes of inflammatory cytokines that are closely associated with CNP[1-3]and compared with oral Western medication. The results are now summarized as follows.

1 Clinical Data

1.1 Diagnostic criteria

This was based on Chinese Diagnosis and Treatment Guidelines for Urological Conditions (2009 edition)[4]: pain mainly in the pelvic area but also in the lower abdomen, lumbosacral region, perineum, testis, penis or above the pubic bone; urgency, frequency or dribbling of urination, presence of white secretion after urination and difficult urination.

The symptom scores were evaluated according to the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI).

1.2 Inclusion criteria

Those who met the above diagnostic criteria; aged between 40 and 60 years; CNP duration lasted 6-12 months.

1.3 Exclusion criteria

Having complications of urinary tract infection, inflammation involving the reproductive system, varicocele, irritable bowel syndrome, urogenital tuberculosis, urinary stones, urethral stricture or neurogenic cystitis; having complications of prostate cancer or hyperplasia.

1.4 Statistical methods

1.5 General materials

A total of 80 CNP cases treated at our Center between January 2012 and April 2014 were randomly allocated into an observation group and a control group according to their visiting sequence. There were no between-group statistical differences in age, duration and NIH-CPSI score (P＜0.05), indicating that the two groups were comparable (Table 1).

Table 1. Between-group comparison of general materials

2 Treatment Methods

2.1 Observation group

2.1.1 Western medication

Patients took 0.2 mg of Tamsulosin Hydrochloride Sustained Release Capsules (Harnal) manufactured by Astellas Pharma Inc. (China, China Food and Drug Administration approval number: 20000681) for each dose, 1 dose a day for 28 d.

2.1.2 Ginger-partitioned moxibustion

Points: Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), bilateral Zusanli (ST 36), Sanyinjiao (SP 6), Pangguangshu (BL 28), Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34).

Method: The patient took a supine lying position. The practitioner placed the ginger powder (round shape of 3 cm in thickness) over Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), and bilateral Zusanli (ST 36) and Sanyinjiao (SP 6). Then, placed a moxa cone (manufactured by Hubei Li Shizhen Genuine Materia Medica Co., Ltd.) of 1.8 cm in diameter and 2.6 cm in height above the ginger powder on each point. Ignited the moxa cone and removed ashes and ginger powder when the moxa cones were burnt out. After this, the patient was changed to a prone lying position, the practitioner applied same method to bilateral Pangguangshu (BL 28), Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34). The treatment was done once a day, for 28 d.

2.2 Control group

3 Results Observation

3.1 Measurement parameters

3.1.1 T cell subsets

A total of 10 mL venous blood was extracted before and the next morning after treatment and then stored at a temperature of －20℃ after serum separation. Then the CD3+, CD4+and CD8+were detected using direct MCAB-A-E method. The regents were provided by Beijing Bole Life Science Development Co., Ltd.

3.1.2 Detection of CD4+CD25+, CD4+CD25+Foxp3 and TGF-β1

Some of the collected samples were made into single-cell suspension. Then the cell counts of CD4+CD25+and CD4+CD25+Foxp3+were detected using the flow cytometer. The rest of the samples were conducted anti-freezing management, followed by centrifugation for 10-minute at 2 000 r/min to separate plasma. Then, placed the plasma into an epikote (EP) tube and stored at refrigerator (－70℃). The TGF-β1 concentration was detected using enzyme-linked immunosorbent assay (ELISA) kit.

3.1.3 Detection of immuneglobulin (Ig)

The IgA, IgE, IgG and IgM levels in both groups were detected using ELISA method before and after treatment. The ELISA kits were manufactured by Dongxiyi (Beijing) Science & Technology Co., Ltd.

3.2 Therapeutic efficacy evaluation

The symptoms were scored using the NIH-CPSI. Then the therapeutic efficacy was evaluated by the NIH-CPSI scores.

Clinical recovery: Alleviation of clinical symptoms or NIH-CPSI score was decreased by ≥90%.

Marked effect: The NIH-CPSI score was decreased by≥50% but ＜90%.

Improvement: The NIH-CPSI score was decreased by≥25% but ＜50%.

Failure: The decrease of NIH-CPSI score was ＜25%.

3.3 Results

3.3.1 Clinical effects

The total effective rate was 90.0% in the observation group, versus 72.5% in the control group, showing a statistical differences (P＜0.05) and a better effect in the observation group than that in the control group (Table 2).

3.3.2 Changes of CD3+, CD4+and CD8+in peripheral blood

After treatment, the CD3+, CD4+and CD8+in peripheral blood T cells in both groups were significantly increased (P＜0.05). There were betweengroup statistical differences in CD3+, CD4+and CD8+(P＜0.05), showing a more significant effect in the observation group than that in the control group (Table 3).

3.3.3 Changes of CD4+CD25+, CD4+CD25+Foxp3+and TGF-β1 contents

After treatment, the CD4+CD25+, CD4+CD25+Foxp3+and TGF-β1 contents in peripheral blood T cells were significantly increased in both groups (P＜0.05). There were between-group statistical differences in CD4+D25+, CD4+CD25+Foxp3+and TGF-β1 contents (P＜0.05), showing a better effect in the observation group than that in the control group (Table 4).

3.3.4 Changes of serum IgA, IgE, IgG and IgM

After treatment, the contents of IgA, IgG and IgM in both groups were significantly increased and the IgE content in both groups was significantly decreased (P＜0.05). There were between-group statistical differences in IgA, IgE, IgG and IgM (P＜0.05), showing a more significant change in the observation group than that in the control group (Table 5).

3.3.5 Changes of NIH-CPSI scores

After treatment, the total NIH-CPSI scores and pain discomfort scores in both groups were significantly decreased (P＜0.05). There were between-group statistical differences in total NIH-CPSI score and pain and discomfort score (P＜0.05), showing a more significant effect in the observation group than that in the control group (Table 6).

Table 2. Between-group comparison of clinical effects (case)

Table 3. Between-group comparison of T-cell subsets in peripheral blood

Table 3. Between-group comparison of T-cell subsets in peripheral blood

Note: Intra-group comparison before and after treatment, 1) P＜0.05; inter-group comparison after treatment, 2) P＜0.05

Group n Time CD3+CD4+CD8+Observation 40 Before treatment 31.31±6.04 23.49±6.05 18.73±4.66 After treatment 60.60±12.001)2)60.30±12.771)2)50.20±10.761)2)Control 40 Before treatment 30.74±5.96 23.07±6.15 19.08±5.53 After treatment 47.55±11.71)49.20±10.221)35.70±8.571)

Table 4. Between-group comparison of CD4+CD25+, CD4+CD25+Foxp3+and TGF-β1 contents

Table 4. Between-group comparison of CD4+CD25+, CD4+CD25+Foxp3+and TGF-β1 contents

Note: Intra-group comparison before and after treatment, 1) P＜0.05; inter-group comparison after treatment, 2) P＜0.05

Group n Time CD4+CD25+(%) CD4+CD25+Foxp3+(%) TGF-β1 (pg/mL) Observation 40 Before treatment 2.49±0.86 2.76±0.92 66.90±20.80 After treatment 5.11±1.081)2)4.84±1.521)2)162.70±39.201)2)Control 40 Before treatment 2.45±0.93 2.69±0.78 70.80±19.30 After treatment 3.88±1.131)3.61±1.441)127.1±40.11)

Table 5. Between-group comparison of IgA, IgE, IgG and IgM contents

Table 5. Between-group comparison of IgA, IgE, IgG and IgM contents

Note: Intra-group comparison before and after treatment, 1) P＜0.05; inter-group comparison after treatment, 2) P＜0.05

Group n Time IgA (g/L) IgE (ng/L) IgG (g/L) IgM (g/L) Observation 40 Before treatment 4.85±0.96 261.30±39.50 7.56±1.20 4.71±1.20 After treatment 8.13±1.151)2)125.70±29.401)2)11.18±1.331)2)6.93±1.441)2)Control 40 Before treatment 4.91±1.12 250.10±34.20 7.61±1.27 4.67±1.06 After treatment 6.88±1.211)170.10±33.101)9.41±1.041)5.50±1.251)

Table 6. Between-group comparison of NIH-CPSI scores

Table 6. Between-group comparison of NIH-CPSI scores

Note: Intra-group comparison before and after treatment, 1) P＜0.05; inter-group comparison after treatment, 2) P＜0.05

Group n Total score Pain and discomfort score Before treatment After treatment Before treatment After treatment Observation 40 21.32±5.14 11.19±5.411)2)15.92±3.46 7.20±3.411)2)Control 40 22.94±7.52 15.62±3.601)16.13±4.20 10.54±5.091)

4 Discussion

The development of CNP is closely associated with lymphocyte regulation. T cell plays a central role in cell-mediated immunity. It’s known that CD4+cells can synthesize interleukin (IL)-4 and IL-13 and increase the IgE synthesis of B lymphocytes[5-6]; CD8+cells can synthesize interferon (IFN)-γ, inhibit IgE synthesis induced by IL-4 and IL-13 and result in imbalance of T-cells and their subsets in early CNP[7-8]. Experimental studies have shown that CNP patients have significantly lower transforming growth factor (TGF)-β. TGF-β can induce Foxp3 (CD4+CD25+regulatory T cells) positive and prevent allergic reaction. Studies have proven that hormone can up-regulate Foxp3, increase differentiation of CD4+CD25+and regulatory T cells and thus achieve therapeutic effects. Evidently, abnormal Foxp3 (CD4+CD25+regulatory T cells) is associated with the onset of CNP[9-11]. In addition, low levels of IgA, IgG and IgM in CNP patients may cause a poor resistance of the respiratory tract mucosa to virus, bacteria or other pathogenic microorganisms and make the patients susceptible to infection[12-14].

Numerous studies have confirmed the role of moxibustion in the prevention and treatment of prostatitis[15-18]. In this study, Guanyuan (CV 4) is the origin of Conception, Governor and Thoroughfare Vessels. It is the house of Yuan-Primordial qi where the seminal fluids are stored. In addition, this point is a crossing point of the Conception Vessel with the Liver, Spleen and Kidney Meridians as well as the Front-Mu point of the small intestine. As a key point for deficiency and consumption, Guanyuan (CV 4) can be used to treat frequency of urination, enuresis, urine retention, bloody urine, nocturnal emissions, impotence, gonorrhea and pain or blood stasis in the lower abdomen. Zhongji (CV 3), the Front-Mu point of the urinary bladder, is combined to cultivate Yuan-Primordial qi, resolve dampness and clear heat; Pangguangshu (BL 28) to harmonize meridian qi and blood; Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao (BL 34) to tonify kidney yang and relieve water retention; Zusanli (ST 36) to supplement anti-pathogenic qi; and Sanyinjiao (SP 6) to regulate and facilitate qi of three yin meridians of foot. The above points combined can tonify the spleen and kidney, resolve dampness and stasis, clear heat and invigorate blood[19-21].

The study findings have shown that gingerpartitioned moxibustion can increase the levels of CD3+, CD4+, CD8+, CD4+CD25+, CD4+CD25+Foxp3 and TGF-β1 as well as the contents of IgA, IgG and IgM and decrease the IgE content. This indirectly proves that gingerpartitioned moxibustion can boost the immune response, control chronic infection and thus prevent CNP. In addition, the convenient ginger-partitioned moxibustion has no adverse reactions and is worthy of further clinical application.

Conflict of Interest

The authors declared that there was no conflict of interest in this article.

Acknowledgments

This work was supported by Hebei Tangshan Science & Technology Program (河北省唐山市科技計劃項目, No. 121302118b).

Statement of Informed Consent

Informed consent was obtained from all individual participants included in this study.

Received: 28 September 2014/Accepted: 12 November 2014

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Translator: Han Chou-ping (韓丑萍)

隔姜灸對慢性非細菌性前列腺炎患者免疫細胞因子的影響

目的：觀察隔姜灸對慢性非細菌性前列腺炎患者免疫細胞因子的影響。方法：將慢性非細菌性前列腺炎患者80例，按就診順序隨機分為兩組，每組40例。觀察組予口服鹽酸坦索羅辛緩釋膠囊(哈樂) (Tamsulosin Hydrochloride Sustained Release Capsules, Harnal)，每次0.2 mg，每日 1 次；隔姜灸氣海、關(guān)元、中極及雙側(cè)足三里、三陰交、膀胱俞、上髎、次髎、中髎和下髎治療, 每日1次。對照組僅口服鹽酸坦索羅辛緩釋膠囊，劑量及服用方法與觀察組相同。兩組均治療28 d。治療前、后檢測患者外周血中CD3+、CD4+、CD8+、CD4+CD25+、CD4+CD25+Foxp3+、轉(zhuǎn)化生長因子-β1 (transforming growth factor-β1, TGF-β1)、免疫球蛋白(immuneglobulin, Ig) A、IgE、IgG和IgM，并進行美國國立衛(wèi)生研究院慢性前列腺炎癥狀指數(shù)(National Institutes of Health chronic prostatitis symptom index, NIH-CPSI)評分。結(jié)果：觀察組總有效率90.0%；對照組總有效率72.5%，兩組總有效率差異有統(tǒng)計學(xué)意義(P＜0.05)。治療后，兩組患者CD3+、CD4+、CD8+、CD4+CD25+、CD4+CD25+Foxp3+、TGF-β1、IgA 、IgG及IgM均明顯提高，與本組治療前差異有統(tǒng)計學(xué)意義(P＜0.05)；觀察組CD3+、CD4+、CD8+、CD4+CD25+、CD4+CD25+Foxp3+、TGF-β1、IgA、IgG、IgE、IgM、NIH-CPSI總分及疼痛與不適評分與對照組有統(tǒng)計學(xué)差異(P＜0.05)。結(jié)論：隔姜灸可通過提高免疫功能改善慢性非細菌性前列腺炎患者的臨床癥狀。

前列腺炎; 灸法; 間接灸; 隔姜灸; 免疫

R245.8 【

】A

in the control group only

oral Western medication (same dose and treatment course as those in the observation group).

Author: Li Guo-dong, attending physician

Li Shu-yi, master of medicine, vice chief analyst, attending physician.

E-mail: liqi19801211@163.com