ARDINATA D, ZAIN-HAMID R, MAHADI I D, et al.

Reduction of serum level of interleukin-2 and pruritus severity after

acupuncture at Quchi (LI11) in hemodialysis patients: a placebo-controlled randomized clinical trial. J Acupunct Tuina Sci, 2022, 20(2):
126-133
DOI: https://doi.org/10.1007/s11726-022-1299-3

Clinical Study

Reduction of serum level of interleukin-2 and

pruritus severity after acupuncture at Quchi (LI11) in
hemodialysis patients: a placebo-controlled
randomized clinical trial
针刺曲池穴降低血液透析患者血清白介素2和瘙痒: 安慰剂随机对照临床试验
Dedi ARDINATA1, Rozaimah ZAIN-HAMID2, Irma D MAHADI3, Hasan MIHARDJA4
1 Department of Physiology, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
2 Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
3 Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia
4 Department of Medical Acupuncture, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia

Abstract
Objective: To observe the effect of acupuncture at Quchi (LI11) on the serum interleukin-2 (IL-2) level and the severity
of uremic pruritus (UP) in hemodialysis patients.
Methods: Sixty hemodialysis patients with UP were randomized into an acupuncture group and a control group, with
30 cases in each group. In the acupuncture group, patients were treated with acupuncture at Quchi (LI11) twice a week
for six weeks. In the control group, each patient received a placebo treatment (sham acupuncture). Before and after
the intervention, the pruritis severity was examined using a 5-D scale, and the serum IL-2 level was measured using an
enzyme-linked immunosorbent assay kit.
Results: There were no statistically significant differences in the demographic or clinical factors between the control
group and the acupuncture group at baseline. The reduction in pruritus severity in patients was more significant in the
acupuncture group (P=0.027). Acupuncture therapy also significantly decreased the serum IL-2 level in the patients
(P=0.011). Throughout the acupuncture procedures, the incidence of pain and mild bleeding was 3.6% and 2.5%,
respectively.
Conclusion: Six-week acupuncture treatment at Quchi (LI11) can effectively decrease the severity of UP and the serum
IL-2 level. Large-scale, long-duration, and multi-center studies are needed to fully understand the role of IL-2 in
inflammation and neuroimmune stimulation during acupuncture.
Keywords: Acupuncture Therapy; Point, Quchi (LI11); Interleukin-2; Pain; Pruritus; Hemodialysis; Randomized Controlled Trial
【摘要】目的: 观察针刺曲池穴对血液透析患者血清白细胞介素2(IL-2)水平及尿毒症瘙痒(UP)程度的影响。方法: 将60
例尿素症瘙痒的血液透析患者随机分为针刺组和对照组, 每组30例。针刺组患者接受针刺曲池治疗, 每周2次, 共治
疗6周。对照组患者接受安慰剂治疗(假针刺)。干预前后用5-D量表评价瘙痒程度, 用酶联免疫吸附测定试剂盒检测血
清IL-2水平。结果: 在人口统计及临床因素方面对照组与针刺组基线数据无统计学差异。针刺组患者的瘙痒减轻程度
明显高于对照组(P=0.027)。同时, 针刺疗法能显著降低血清IL-2水平(P=0.011)。全部针刺过程中, 疼痛和轻微出血的
发生率分别为3.6%和2.5%。结论: 针刺曲池6周有效地降低了UP严重程度及血清IL-2水平。为全面了解针刺时IL-2在炎
症和神经免疫刺激中的作用, 需要开展大样本、长周期、多中心的研究。
【关键词】针刺疗法; 穴, 曲池; 白细胞介素2; 疼痛; 瘙痒; 血液透析; 随机对照试验
【中图分类号】R246.1 【文献标志码】A

A large number of patients on dialysis are
experiencing pruritus[1-2]. The pathogenesis of uremic
pruritus (UP) in patients undergoing hemodialysis is not
fully understood; however, the immune-mediated
hypothesis generally forms the basis for pruritic
treatment[3-4]. Several studies suggest that renal failure
Author: Dedi ARDINATA, M.D. E-mail: dedi1@usu.ac.id
● 126 ●︱© Shanghai Research Institute of Acupuncture and Meridian 2022
may be associated with the build-up of pro-
inflammatory compounds[3-10]. Interleukin-2 (IL-2) is a
key cytokine in the cell-mediated immune response. It
has been known to induce pruritus; indeed, an increase
in the number of immune-reactive IL-2 cells has been
observed in pruritic psoriasis lesions compared with
non-pruritic ones[11-12]. The pruritogenic role of IL-2 has
also been discovered in cancer treatment[13-16].
J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133
Corticosteroids, antibiotics, calcineurin inhibitors,
ultraviolet (U.V.) phototherapy, and systemic
immunomodulating therapies are generally used to
treat pruritus[8,17-19]. However, due to the possible side
effects of these approaches, there is a growing interest
in complementary medicine. Significant reduction in
pruritus severity after acupuncture therapy at Quchi
(LI11) has recently been reported[11,20-22]. GAO H, et al[23]
reported that stimulation to Quchi (LI11) and Zusanli
(ST36) resulted in 97% healing in one month. CHOU C Y,
et al[24] reported that stimulation Quchi (LI11) alone for
1 h, three times a week for one month, significantly
reduced pruritic scores in hemodialysis patients.
Another study reported that stimulating Quchi (LI11) for
1 h, twice a week for 12 times, significantly reduced
pruritis scores[25]. A systematic review of the efficacy of
acupuncture for treating UP in patients with end-stage
renal disease has revealed that most reported studies
have a high risk of bias, underscoring the need for more
studies to confirm the beneficial effects of
acupuncture[26]. Furthermore, to the best of our
knowledge, the effects of acupuncture on the IL-2 level
in patients with UP have not been examined yet.
This paper reports a randomized controlled trial. The
first objective of this study is to validate the efficacy of
acupuncture therapy in relieving pruritus among
hemodialysis patients. The second objective is to
examine the serum level of IL-2 in the patients before
and after acupuncture therapy.
1 Clinical Materials
1.1 Research design
A randomized controlled trial (RCT) was conducted in
the Hemodialysis Unit of Kidney Installation and
Hypertension in General Hospital H. Adam Malik Medan.
The study compared two groups. The subjects in the
acupuncture group received acupuncture at Quchi
(LI11), whereas, in the control group, the subjects
received a placebo treatment. Procedures were
conducted following the Standards for Reporting
Interventions in Clinical Trials of Acupuncture (STRICTA),
(Table 1)[27]. Certified doctors of the Indonesian
Acupuncture Doctors Association (PDAI) with more than
two years of experience performed the procedures.
1.2 Subjects
Subjects meeting the inclusion criteria were enrolled
by consecutive sampling and randomly assigned to two
groups. A web application available at
https://www.randomizer.org/ was used for
randomization. The subjects in the acupuncture group
received acupuncture therapy, and the control group
received a placebo treatment (Figure 1).
The inclusion criteria involved men and women over
the age of 18 years who have receiving hemodialysis
twice a week for more than six months and were
© Shanghai Research Institute of Acupuncture and Meridian 2022︱● 127
hemodynamically stable; patients who have never
received acupuncture therapy; those with mental and
physical soundness and with the ability to respond to
the questionnaire. The patients on drugs that affect
pruritus or those in drug washout periods were
excluded. The sample size was calculated using G*
Power 3.1.9.2 (24), with effect size = 0.8; (err prob)
α=0.05 and Power [1 - (err prob) β] = 0.90. A minimum
of 28 patients in each group were required. Health
Research Ethics Commission (KEPK) Faculty of Medicine,
Universitas Sumatera Utara, and General Hospital H.
Adam Malik Medan, Indonesia approved the trial
protocol (No. 455/TGL/KEPK FK USU-RSUP HAM/2018).
This experiment was carried out under the principles of
the Declaration of Helsinki (Edinburgh 2000 Version).
Participation in the study was voluntary. All subjects
signed an informed consent form before the research
procedure was carried out (Informed consent code:
RM.2.11/IC. Study/2018).
1.3 Baseline characteristics
Age, sex, ethnicity, primary disease, body mass index
(BMI) after hemodialysis, quantitative C-reactive protein
(CRP), duration of hemodialysis, urea reduction ratio
(URR), hemoglobin, the pruritus score, and serum IL-2
level were recorded for all patients.
1.4 Pruritic test
The pruritic test was conducted using the Indonesian
version of a 5-D scale[28]. The 5-D scale is a quantitative
assessment of multidimensional pruritis experienced by
pruritic patients. The assessment covers the following
aspects: duration, intensity, development, disruption of
activity, and the itching location. The questionnaire
rates the responses on a scale between 5 and 25 points.
The pruritic scale assessment was carried out on all
subjects by a nurse trained and blinded to the grouping.
1.5 IL-2 measurement
The serum IL-2 level was measured by a commercially
available enzyme-linked immunosorbent assay kit (Cat.
No. EH0189, Fine Test®, Wuhan, Hubei, China),
according to the manufacturer's instructions. The
characteristics of the kit are as follows. Detection range:
15.6-1 000 pg/mL; sensitivity: <9.375 pg/mL; precision:
intra-assay coefficient of variation (CV) <8% and
inter-assay CV <10%. The subjects’ vein blood
specimens were taken before the hemodialysis
procedure was performed. The samples were allowed
to clot for 2 h at room temperature or overnight at 4 ℃
before centrifuged for 20 min at approximately 1 000 g.
The supernatant was collected, and the assay was
carried out immediately. Blood was collected using
disposable, non-pyrogenic, and non-endotoxin tubes
and stored at -40 ℃ until testing.
1.6 Intervention
The hemodialysis lasted for 1 h if the hemodynamic
condition was stable. This was followed by cleaning and
sterilizing the Quchi (LI11) areas. The point selection
●
 J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133

was based on the criteria in the Medical Acupuncture: A
Western Scientific Approach[29]. Each subject in the
acupuncture group was punctured perpendicularly
using sterile, disposable, single-use, and stainless-steel
needles (0.25 mm in diameter and 25 mm in length, Bai
Yi Mei®). The needle was inserted as deep as 1.0-1.5 cm
into Quchi (LI11). The needle insertion point was
adjacent to the needle punctured for the hemodialysis
procedure, and the acupuncture needle was retained
for 1 h[25]. Each subject in the control group was given a
placebo treatment with needles of the same
specification as in the acupuncture group affixed
(without puncture) to the skin surface at Quchi (LI11)
with the help of plasters [22 mm in diameter; round
adhesive wound plaster, Henso® (Healthaw Medical
Limited, China)] and retained for 1 h. The patients did
not report any itching or discomfort after the
application of the plaster. Figure 2 shows the
arrangements used in the control group and the
acupuncture group. Quchi (LI11) is located on the lateral
side of the elbow, at the middle between Chize (LU5)
and the lateral humeral epicondyle. If the elbow joint is
in a state of maximal flexion, Quchi (LI11) is pointed at
the tip of the fold of the lateral elbow line[30]. All actions
in the acupuncture group and the control group were
carried out twice a week for six weeks[25]. An evaluation
of the side effects of acupuncture and control was
carried out.
1.7 Outcome variables
The primary outcome was the relative change in the
pruritic scale from the baseline till six weeks later. The
secondary outcomes were the change in the serum IL-2
level and side effects of the intervention such as pain
and bleeding. The visual analog scale (VAS) was used to
measure the pain experienced by patients after the
treatment.

Table 1. STRICTA checklist, detail of intervention (2010)

Item Details
Style of acupuncture Manual acupuncture based on Medical Acupuncture: A Western Scientific
Approach[29]
The reasoning for treatment provided, based The acupoint used in this study was Quchi (LI11), located at the elbow.
Acupuncture
on historical context, literature sources, and/or According to a systematic review and meta-analysis of randomized controlled
rationale
consensus methods, with references wherever clinical trials of itch (YU C, et al)[31], Quchi (LI11) is one of the most
appropriate frequently used acupuncture points for pruritic therapy
The extent to which treatment was varied All participants received the same treatment
Number of needle insertions per subject per 1
session
Names of points used Quchi (LI11) on the affected side
Depth of insertion, based on a specified unit of 1.0-1.5 cm
Details of measurement
needling Response sought Needling sensation (Deqi)
Needle stimulation Manual acupuncture
Needle retention time 1h
Needle type Placebo acupuncture needle; a stainless steel needle, 0.25 mm in diameter and
25 mm in length, Bai Yi Mei®
Treatment Number of treatment sessions 12
regimen Frequency and duration of treatment sessions Twice per week, 1 h per session
Details of other interventions administered to None
Other the acupuncture group
components Setting and context of treatment, including The study conducted in the Hemodialysis Unit of Kidney Installation and
of treatment instructions to practitioners, and information Hypertension in General Hospital H. Adam Malik Medan, and all information
and explanations to patients was provided to the subjects
Practitioner Description of participating acupuncturists The certified doctors of the Indonesian Acupuncture Doctors Association
background (PDAI) with more than two years of experience performed the procedures
Rationale for the control or comparator in the Superficial entry (WONG E L, et al)[32]. Quchi (LI11), unilateral, adjacent to
Control or context of the research question, with sources needle punctured in the hemodialysis procedure. Affixed (without puncture) to
comparator that justify this choice the skin surface at Quchi (LI11) point with the help of plasters to prevent
interventions drop-off; needle retention time: 1 h; placebo acupuncture needle; stainless steel
needles, 0.25 mm in diameter and 25 mm in length, Bai Yi Mei®
Note: STRICTA=Standards for Reporting Interventions in Clinical Trials of Acupuncture

● 128 ●︱© Shanghai Research Institute of Acupuncture and Meridian 2022

J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133

Enrollment Assessed for eligibility (n=60)

Randomized (n=60)

Allocation
Allocated to the intervention group Allocated to the control group and
and received allocated intervention received allocated intervention
(n=30) (n=30)

Analysis
Analysed (n=30) Analysed (n=30)
Excluded from analysis (n=0) Excluded from analysis (n=0)

Figure 1. Flow chart of the study

Acupuncture group Control group

Note: The arrow points to the plaster
Figure 2. Interventions in the two groups

1.8 Statistical analysis 2 Results

All data were analyzed using SPSS version 17.0
statistical software. Mean ± standard deviation ( x ±s)
was calculated for normally distributed data, and
median (minimum, maximum) [M (min, max)] was
calculated for non-normally distributed or skewed
continuous data. Categorical data were presented in
numbers. The t-test was used for the comparison of
normally distributed data, and the Mann-Whitney
U-test (non-parametric test) was used for the
comparison of skewed continuous data between the
acupuncture group and control group. The Pearson
correlation test was used for assessing the strength of
the correlation between normally distributed data. The
statistical significance was set at P<0.05.
2.1 Baseline characteristics
A total of 60 subjects were included in this study and
were allocated randomly to an acupuncture group and
a control group. At baseline, the two groups were not
statistically different in terms of characteristics such as
gender, age, duration of hemodialysis, ethnicity, or
comorbidities (Table 2 and Table 3).
The prevalence of comorbidities such as
hypertension, diabetic nephropathy, and infection, and
obstructive kidney disease was also statistically equal
between the two groups.

© Shanghai Research Institute of Acupuncture and Meridian 2022︱● 129 ●

 J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133

Table 2. Baseline demographic characteristics of the patients

Acupuncture group Control group Statistical
Demography P-value
(n=30) (n=30) value
Male 22 22
Gender (case) 0.0011) 1.000
Female 8 8
Age [M (min, max), year] 54.5 (20.0, 67.0) 51.5 (25.0, 77.0) -0.8882) 0.375
20-29 years old 1 7
30-38 years old 3 1
39-47 years old 4 4
Age (case) 48-56 years old 9 7 9.0661) 0.170
57-65 years old 12 7
66-74 years old 1 3
75-83 years old 0 1
Karonese 11 13
Ethnicity Tobanese 9 8
(case) 3.3021) 0.960
Javanese 7 6
Mandailingnese 3 3
Hypertension 15 11
Major
Diabetic nephropathy 10 11 1.3551) 0.508
diseases (case)
Infection and obstructive kidney disease 5 8
Note: 1) Chi-square test, χ2-value; 2) Mann-Whitney U-test, Z-value

Table 3. Comparison of the key clinical parameters at baseline

Acupuncture group Control group Statistical
Factor P-value
(n=30) (n=30) value
BMI [M (min, max), kg/m2] 23.41 (16.44, 37.18) 23.54 (17.69, 28.13) -0.7691) 0.442
1)
CRP [M (min, max), mg/dL] 0.35 (0.35, 1.40) 0.35 (0.35, 2.80) -0.456 0.648
Duration of hemodialysis ( x ±s, month) 38.73±19.98 35.63±16.97 0.648 2)
0.520
URR ( x ±s) 0.70±0.07 0.69±0.70 0.280 2)
0.780
Hemoglobin ( x ±s, g/dL) 9.30±1.50 9.52±1.38 -0.6002) 0.551
Creatinine ( x ±s, mg/dL) 15.22±3.79 15.84±4.19 -0.601 2)
0.550
IL-2 ( x ±s, pg/mL) 105.66±94.24 99.40±92.55 0.010 2)
0.802
Pruritus score ( x ±s, point) 16.30±4.15 16.83±3.97 -0.538 2)
0.613
Note: 1) Mann-Whitney U-test, Z-value; 2) Unpaired t-test, t-value; BMI=Body mass index; CRP=C-reactive protein; URR=Urea reduction
ratio; IL-2=Interleukin 2

2.2 Effect of therapy (13.83±4.82), (P=0.023). The decrease, however, was

All patients completed the course of treatment. The
mean serum IL-2 level decreased in the acupuncture
group from (105.99±99.24) pg/mL at baseline to
(51.59±37.95) pg/mL after acupuncture (P=0.007).
There was no significant change in the IL-2 level in the
control group (P=0.852). The unpaired t-test revealed a
significant difference in the mean serum IL-2 level
between the acupuncture group and control group
after six weeks of treatment (P=0.011), (Figure 3).
The mean pruritus score in the acupuncture group
decreased from (16.30±4.15) to (11.43±3.23), (P=0.000)
after six weeks of acupuncture. In the control group, the
mean pruritus score decreased from (16.83±3.97) to
more pronounced in the acupuncture group than in the
control group (P=0.027), (Figure 4).
2.3 Correlation between the pruritus score and IL-2
level
A significant positive correlation was observed
between the serum IL-2 level and pruritus score at
baseline and after six weeks of treatment (Table 4).
2.4 Adverse effects
The side effects of Quchi (LI11) acupuncture included
pain in 3.61% of 360 procedures (12 times in
30 subjects) with a mean VAS value of 2.15 and mild
bleeding in 2.50% of 360 procedures.

● 130 ●︱© Shanghai Research Institute of Acupuncture and Meridian 2022

J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133
Note: Intra-group comparison, 1) P=0.007; compared with the
control group after six weeks, 2) P=0.011
Figure 3. Comparison of the serum IL-2 level
Note: Intra-group comparison, 1) P=0.000, 2) P=0.023;
compared with the control group after six weeks, 3) P=0.027
Figure 4. Comparison of the change in the pruritus score
Table 4. Correlation between the serum IL-2 level and
pruritus score after six weeks of intervention
Correlation r r2 P-value
Baseline 0.350 0.123 0.029
After six weeks 0.278 0.077 0.031
3 Discussion
Pruritis is one of the common complications of
dialysis, significantly affecting the quality of life of
patients[19]. This RCT indicates that, in patients
undergoing hemodialysis, acupuncture can reduce the
severity of pruritus and the serum IL-2 level. Our results
are consistent with the studies conducted by CHOU C Y,
et al[24] and PHAN F A, et al[25], in which, a significant
decrease in pruritis after acupuncture was reported.
Quchi (LI11) is a commonly used acupuncture point
for the treatment of skin disorders[33-34]. Pruritus is
associated with the disharmony between the mu- and
kappa-receptors[35-36]. In the context of traditional
medicine, acupuncture at Quchi (LI11) can drain damp,
cool blood, eliminate wind, and alleviate itching[37].
Essentially, insertion of acupuncture needles in Quchi
(LI11) stimulates the radial nerve, median nerve, and
brachioradialis extensor carpi radialis longus muscle.
This stimulation generates signals from the sensory
© Shanghai Research Institute of Acupuncture and Meridian 2022︱● 131
afferent somatic nerves that are transmitted to the
spinal cord in the C5, C6, and C7 segments[38-39]. Signals
from the vagus efferent nerve fibers spread to the celiac
ganglia in the celiac plexus where the splenic nerve
originates. The splenic nerve releases norepinephrine,
which affects cytokine production, such as IL-2, by
different mechanisms[40-44].
DA SILVA M D, et al[45] found acupuncture to reduce
the levels of pro-inflammatory cytokines. On the other
hand, an intradermal injection of IL-2 was reported to
induce pruritus and erythema, both in healthy and
atopic dermatitis patients[11]. The administration of high
doses of IL-2 in patients with certain malignancies was
also reported to induce intense pruritus[14-16]. IL-2
activates Treg cells to produce inflammatory cytokines
tumor necrosis factor-α (TNF-α) and interferon-γ
(IFN-γ)[21-22,46-49]. The reduction in IL-2 level is, therefore,
expected to contribute to the reduced severity of
pruritus. More studies are needed to provide detailed
mechanism insight into the change of IL-2 level and
their subsequent impact on pruritus in the context of
acupuncture therapy.
In the present study, pain and bleeding were the
reported side effects of acupuncture at Quchi (LI11).
Transient pain is generally experienced when the
acupuncture needle is inserted, and minor bleeding
may occur during the needle extraction. Other less
commonly reported side effects are internal organs,
tissue, or nerve injuries[49-50]. In our study, no such
complications were observed; however, proper safety
precautions must be in place for acupuncture. A
decrease in UP severity was also observed in the control
group, suggesting psychological inducements[35,51]. The
level of decrease was considerably lower compared
with the acupuncture group, and there was no
significant change in the IL-2 level.
This study has several limitations. First, it is a
single-center study; a multi-center clinical trial will be
necessary for supporting the conclusion of this study.
Achieving a complete placebo effect is another major
limitation[52-53]. Therefore, more randomized controlled
trials with sham control groups are needed to fully
corroborate our results. We have currently focused on
IL-2; however, it is also important to elucidate the role
of other mediating agents. Furthermore, the study did
not include a follow-up or treatment at multiple time
points; further studies with a long-term follow-up may
help develop a standardized treatment protocol.
4 Conclusion
In this RCT, acupuncture at the single Quchi (LI11)
acupoint, 12 times over six weeks, was found to be an
easy, safe, and effective modality to manage UP in
hemodialysis patients. Acupuncture therapy also
reduced the serum IL-2 level, and there was a
●

correlation between the serum IL-2 level and the
severity of pruritus. Further exploration of the
underlying mechanism will improve the understanding
of the role of IL-2 in post-acupuncture alleviation of
pruritis in hemodialysis patients.
Conflict of Interest
The authors declare that there is no potential conflict of
interest in this article.
Acknowledgments
The authors would like to thank the editors of Editverse
(www.editverse.com) for their help in manuscript editing
and formatting.
Statement of Informed Consent
Informed consent was obtained from all individual
participants.
Received: 19 September 2020/Accepted: 19 April 2021
References
[1] PISONI R L, WIKSTRÖM B, ELDER S J, AKIZAWA T,
ASANO Y, KEEN M L, SARAN R, MENDELSSOHN D
C, YOUNG E W, PORT F K. Pruritus in haemodialysis
patients: international results from the Dialysis Outcomes
and Practice Patterns Study (DOPPS). Nephrol Dial
Transplant, 2006, 21(12): 3495-3505.
[2] MATHUR V S, LINDBERG J, GERMAIN M, BLOCK G,
TUMLIN J, SMITH M, GREWAL M, MCGUIRE D;
ITCH National Registry Investigators. A longitudinal study
of uremic pruritus in hemodialysis patients. Clin J Am Soc
Nephrol, 2010, 5(8): 1410-1419.
[3] ARAMWIT P, OUPPATHAM S. Uremic Pruritus: Its
Prevalence, Pathophysiology and Management. Updates in
Hemodialysis. London: IntechOpen Limited, 2015: 19-42.
[4] SHIRAZIAN S, AINA O, PARK Y, CHOWDHURY N,
LEGER K, HOU L, MIYAWAKI N, MATHUR V S.
Chronic kidney disease-associated pruritus: impact on
quality of life and current management challenges. Int J
Nephrol Renovasc Dis, 2017, 10: 11-26.
[5] MIHAI S, CODRICI E, POPESCU I D, ENCIU A M,
ALBULESCU L, NECULA L G, MAMBET C, ANTON G,
TANASE C. Inflammation-related mechanisms in chronic
kidney disease prediction, progression, and outcome. J
Immunol Res, 2018, 2018: 2180373.
[6] AMORE A, COPPO R. Immunological basis of
inflammation in dialysis. Nephrol Dial Transplant, 2002,
Suppl 8: 16-24.
[7] METTANG T, PAULI-MAGNUS C, ALSCHER D M.
Uraemic pruritus-new perspectives and insights from recent
trials. Nephrol Dial Transplant, 2002, 17(9): 1558-1563.
[8] DILLON S R, SPRECHER C, HAMMOND A,
BILSBOROUGH J, ROSENFELD-FRANKLIN M,
PRESNELL S R, HAUGEN H S, MAURER M, HARDER
B, JOHNSTON J, BORT S, MUDRI S, KUIJPER J L,
BUKOWSKI T, SHEA P, DONG D L, DASOVICH M,
GRANT F J, LOCKWOOD L, LEVIN S D, LECIEL C,
WAGGIE K, DAY H, TOPOUZIS S, KRAMER J,
● 132 ●︱© Shanghai Research Institute of Acupuncture and Meridian 2022
J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133
KUESTNER R, CHEN Z, FOSTER D, PARRISH-NOVAK
J, GROSS J A. Interleukin 31, a cytokine produced by
activated T cells, induces dermatitis in mice. Nat Immunol,
2004, 5(7): 752-760.
[9] YOSIPOVITCH G, DUQUE M I, PATEL T S, ISHIUJI Y,
GUZMAN-SANCHEZ D A, DAWN A G, FREEDMAN B
I, CHAN Y H, CRUMRINE D, ELIAS P M. Skin barrier
structure and function and their relationship to pruritus in
end-stage renal disease. Nephrol Dial Transplant, 2007,
22(11): 3268-3272.
[10] COMBS S A, TEIXEIRA J P, GERMAIN M J. Pruritus in
kidney disease. Semin Nephrol, 2015, 35(4): 383-391.
[11] WAHLGREN C F, TENGVALL LINDER M,
HÄGERMARK O, SCHEYNIUS A. Itch and inflammation
induced by intradermally injected interleukin-2 in atopic
dermatitis patients and healthy subjects. Arch Dermatol
Res, 1995, 287(6): 572-580.
[12] NAKAMURA M, TOYODA M, MOROHASHI M.
Pruritogenic mediators in psoriasis vulgaris: comparative
evaluation of itch-associated cutaneous factors. Br J
Dermatol, 2003, 149(4): 718-730.
[13] GASPARI A A, LOTZE M T, ROSENBERG S A, STERN
J B, KATZ S I. Dermatologic changes associated with
interleukin 2 administration. JAMA, 1987, 258(12): 1624-
1629.
[14] IKOMA A, STEINHOFF M, STÄNDER S,
YOSIPOVITCH G, SCHMELZ M. The neurobiology of
itch. Nat Rev Neurosci, 2006, 7(7): 535-547.
[15] CARR M N, TORRES S M, KOCH S N, REITER L V.
Investigation of the pruritogenic effects of histamine,
serotonin, tryptase, substance P and interleukin-2 in healthy
dogs. Vet Dermatol, 2009, 20(2): 105-110.
[16] BUDDENKOTTE J, STEINHOFF M. Pathophysiology
and therapy of pruritus in allergic and atopic diseases.
Allergy, 2010, 65(7): 805-821.
[17] NOWAK D A, YEUNG J. Diagnosis and treatment of
pruritus. Can Fam Physician, 2017, 63(12): 918-924.
[18] NARITA I, IGUCHI S, OMORI K, GEJYO F. Uremic
pruritus in chronic hemodialysis patients. J Nephrol, 2008,
21(2): 161-165.
[19] METTANG T, KREMER A E. Uremic pruritus. Kidney Int,
2015, 87(4): 685-691.
[20] LEE H C, PARK S Y. Preliminary comparison of the
efficacy and safety of needle-embedding therapy with
acupuncture for atopic dermatitis patients. Evid Based
Complement Alternat Med, 2019, 2019: 6937942.
[21] WANG Z, CHEN T, LONG M, CHEN L, WANG L, YIN N,
CHEN Z. Electro-acupuncture at acupoint ST36
ameliorates inflammation and regulates Th1/Th2 balance in
delayed-type hypersensitivity. Inflammation, 2017, 40(2):
422-434.
[22] LAN L, TAO J, CHEN A, XIE G, HUANG J, LIN J,
PENG J, CHEN L. Electroacupuncture exerts
anti-inflammatory effects in cerebral ischemia-reperfusion
injured rats via suppression of the TLR4/NF-κB pathway.
Int J Mol Med, 2013, 31(1): 75-80.
[23] GAO H, ZHANG W, WANG Y. Acupuncture treatment for
34 cases of uremic cutaneous pruritus. J Tradit Chin Med,
2002, 22(1): 29-30.
[24] CHOU C Y, CHENG Y W, KAO M T, HUANG C C.
Acupuncture in haemodialysis patients at the Quchi (LI11)
J. Acupunct. Tuina. Sci. 2022, 20(2): 126-133
acupoint for refractory uraemic pruritus. Nephrol Dial
Transplant, 2005, 20(9): 1912-1915.
[25] PHAN F A, SRILESTARI A, MIHARDJA H, MARBUN
M B H. Effects of acupuncture on uremic pruritus in
patients undergoing hemodialysis. J Phys Conf Ser, 2018,
1073: 062049.
[26] KIM K H, LEE M S, CHOI S M. Acupuncture for treating
uremic pruritus in patients with end-stage renal disease: a
systematic review. J Pain Symptom Manage, 2010, 40(1):
117-125.
[27] MACPHERSON H, ALTMAN D G, HAMMERSCHLAG
R, LI Y, WU T, WHITE A, MOHER D; STRICTA Revision
Group. Revised standards for reporting interventions in
clinical trials of acupuncture (STRICTA): extending the
CONSORT statement. J Evid Based Med, 2010, 3(3): 140-
155.
[28] ELMAN S, HYNAN L S, GABRIEL V, MAYO M J. The
5-D itch scale: a new measure of pruritus. Br J Dermatol,
2010, 162(3): 587-593.
[29] FILSHIE J, WHITE A, CUMMINGS M. Medical
Acupuncture: A Western Scientific Approach. 2nd Edition.
London: Elsevier Ltd., 2016.
[30] KIM J, OH H J, YOON S P. A cadaveric study of needle
insertion at LI11. Acupunct Med, 2015, 33(6): 497-499.
[31] YU C, ZHANG P, LÜ Z T, LI J J, LI H P, WU C H, GAO F,
YUAN X C, ZHANG J, HE W, JING X H, LI M. Efficacy
of acupuncture in itch: a systematic review and
meta-analysis of clinical randomized controlled trials. Evid
Based Complement Alternat Med, 2015, 2015: 208690.
[32] WONG E L, LEUNG P C, ZHANG L. Placebo
acupuncture in an acupuncture clinical trial. How good is
the blinding effect?. J Acupunct Meridian Stud, 2015, 8(1):
40-43.
[33] PFAB F, HAMMES M, BÄCKER M, HUSS-MARP J,
ATHANASIADIS G I, TÖLLE T R, BEHRENDT H,
RING J, DARSOW U. Preventive effect of acupuncture on
histamine-induced itch: a blinded, randomized, placebo-
controlled, crossover trial. J Allergy Clin Immunol, 2005,
116(6): 1386-1388.
[34] QI Y Z. Unexpected massive cutaneous pruritus treated by
acupuncture. World J Acupunct Moxibustion, 2012, 22(4):
65-66.
[35] KARJALIAN F, MOMENNASAB M, YOOSEFINEJAD A
K, JAHROMI S E. The effect of acupressure on the
severity of pruritus and laboratory parameters in patients
undergoing hemodialysis: a randomized clinical trial. J
Acupunct Meridian Stud, 2020, 13(4): 117-123.
[36] KUMAR K, SINGH S. Neuraxial opioid-induced pruritus:
an update. J Anaesthesiol Clin Pharmacol, 2013, 29(3): 303-
307.
[37] DASHTDAR M, DASHTDAR M R, DASHTDAR B,
KARDI K, SHIRAZI M K. The concept of wind in
traditional Chinese medicine. J Pharmacopuncture, 2016,
19(4): 293-302.
[38] WU J, HU Y, ZHU Y, YIN P, LITSCHER G, XU S.
Systematic review of adverse effects: a further step towards
modernization of acupuncture in China. Evid Based
Complement Alternat Med, 2015, 2015: 432467.
[39] PARK H, KIM K. Isolated common femoral artery injury
resulting from blunt military trauma. Mil Med, 2018,
183(11-12): e758-e761.
© Shanghai Research Institute of Acupuncture and Meridian 2022︱● 133
[40] QI Y C, XIAO X J, DUAN R S, YUE Y H, ZHANG X L,
LI J T, LI Y Z. Effect of acupuncture on inflammatory
cytokines expression of spastic cerebral palsy rats. Asian
Pac J Trop Med, 2014, 7(6): 492-495.
[41] PAVLOV V A, TRACEY K J. Neural circuitry and
immunity. Immunol Res, 2015, 63(1): 38-57.
[42] ZIA S, NDOYE A, LEE T X, WEBBER R J, GRANDO S
A. Receptor-mediated inhibition of keratinocyte migration
by nicotine involves modulations of calcium influx and
intracellular concentration. J Pharmacol Exp Ther, 2000,
293(3): 973-981.
[43] KAWASHIMA K, YOSHIKAWA K, FUJII YX,
MORIWAKI Y, MISAWA H. Expression and function of
genes encoding cholinergic components in murine immune
cells. Life Sci, 2007, 80(24): 2314-2319.
[44] PARRISH W R, ROSAS-BALLINA M, GALLOWITSCH-
PUERTA M, OCHANI M, OCHANI K, YANG LH,
HUDSON L, LIN X, PATEL N, JOHNSON S M,
CHAVAN S, GOLDSTEIN R S, CZURA C J, MILLER E J,
AL-ABED Y, TRACEY K J, PAVLOV V A. Modulation of
TNF release by choline requires alpha 7 subunit nicotinic
acetylcholine receptor-mediated signaling. Mol Med, 2008,
14(9-10): 567-574.
[45] DA SILVA M D, GUGINSKI G, WERNER M F, BAGGIO
C H, MARCON R, SANTOS A R. Involvement of
interleukin-10 in the anti-inflammatory effect of Sanyinjiao
(SP6) acupuncture in a mouse model of peritonitis. Evid
Based Complement Alternat Med, 2011, 2011: 217946.
[46] CAPOBIANCO M, CASSIANO G, FURINI A,
STORTI-MELO L, BONINI C, DANTAS MACHADO RL.
Human interleukin 2 (IL-2) promotion of immune regulation
and clinical outcomes: a review. J Cytok Bio, 2016, 1: 2.
[47] FANG J Q, LIU F, SHAO X M, WU Y Y. Effect of
electroacupuncture on carrageenan-induced inflammation,
IL-1beta and TNF-alpha concentrations and their mRNA
expressions in toe tissue in rats. Zhen Ci Yan Jiu, 2007,
32(4): 224-228.
[48] PARK J Y, PARK H J, CHOI Y Y, KIM M H, KIM S N,
YANG W M. Effects of acupuncture on 1-chloro-2,
4-dinitrochlorobenzene-induced atopic dermatitis. Evid
Based Complement Alternat Med, 2013, 2013: 982095.
[49] WU M, CUI J, XU D, ZHANG K, JING X, BAI W.
Neuroanatomical characteristics of deep and superficial
needling using LI11 as an example. Acupunct Med, 2015,
33(6): 472-477.
[50] ERNST E, WHITE A R. Prospective studies of the safety
of acupuncture: a systematic review. Am J Med, 2001,
110(6): 481-485.
[51] TEY H L, WALLENGREN J, YOSIPOVITCH G.
Psychosomatic factors in pruritus. Clin Dermatol, 2013,
31(1): 31-40.
[52] ZASLAWSKI C, ROGERS C, GARVEY M, RYAN D,
YANG C X, ZHANG S P. Strategies to maintain the
credibility of sham acupuncture used as a control treatment
in clinical trials. J Altern Complement Med, 1997, 3(3):
257-266.
[53] LUND I, NÄSLUND J, LUNDEBERG T. Minimal
acupuncture is not a valid placebo control in randomised
controlled trials of acupuncture: a physiologist’s
perspective. Chin Med, 2009, 4: 1.
●