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Serum Levels of Interleukin-2 and Interleukin-2 Soluble Receptor in Patients with Vitiligo

BaşlıkSerum Levels of Interleukin-2 and Interleukin-2 Soluble Receptor in Patients with Vitiligo
Publication TypeJournal Article
Year of Publication2016
AuthorsKasumagic-Halilovic, E, Ovcina-Kurtovic, N, Soskic, S, Helppikangas, H, Ridic, O
JournalBritish Journal of Medicine and Medical Research
Volume13
Issue10
Start Page1
Pagination1-7
Date Published02/2016
Type of ArticleOriginal Research
Abstract

Background: Vitiligo is a common skin disorder characterized by macular depigmentation of the
skin. Although the etiopathogenesis of the disease is still unclear, several studies have shown that
within the cascade of pathogenesis of vitiligo, cytokines play an important role.
Objectives: The aim of our study was to evaluate serum concentrations of interleukin- IL-2 (IL-2)
and interleukin-2 soluble receptor (IL-2 sR) in patients with vitiligo and healthy subjects and also to
asses a possible association between these cytokines and duration of the disease.
Study Design: Case control study.
Place of the Study: The study was carried out in University Clinical Center Sarajevo, Department
of Dermatology and Venereology.
Patients and Methods: Twenty one patients (11 female and 10 male; age range 15-53 years) with
vitiligo and 20 healthy controls (10 female and 10 male; age range 17-52) were enrolled in the
study. c The duration of vitiligo ranged from 2 to 252 months. Ten patients (47.62%) had
generalized, and eleven patients (52.38%) had localized vitiligo Serum concentrations of cytokines 

were measured using enzyme-linked immunoassay techniques.
Results: Both IL-2 (median 22.600 pg/ml, range 20.900-76.100) and IL-2sR (median 76.100 pg/ml,
range 15.700-183.800) in the patient group were significantly higher when compared with that of the
normal controls. When the serum cytokine level in vitiligo group were compared to total disease
duration (Spearman correlation ρ), serum IL-2 was negatively (ρ= -0.000573, P= 0.9980) and IL-2
sR was positively (ρ=0.241, P= 0.2797) correlated with total disease duration, but it is of borderline
significance.
Conclusions: Our results showed hight serum levels of IL-2 and IL2 sR among vitiligo patients
which may highligth a functional role of these cytokines in the pathogenesis of this disease.

Keywords: Vitiligo; serum cytokines; interleukin-2; soluble interleukin-2 receptor.

Full Text

_____________________________________________________________________________________________________
*Corresponding author: E-mail: eminakahalilovic@gmail.com;
British Journal of Medicine & Medical Research
13(10): 1-7, 2016, Article no.BJMMR.23959
ISSN: 2231-0614, NLM ID: 101570965
SCIENCEDOMAIN international
www.sciencedomain.org
Serum Levels of Interleukin-2 and Interleukin-2
Soluble Receptor in Patients with Vitiligo
Emina Kasumagic-Halilovic1*, Nermina Ovcina-Kurtovic1, Samra Soskic1,
Hana Helppikangas1 and Ognjen Ridic2
1Department of Dermatology and Venerology, University Clinical Center Sarajevo, Sarajevo,
Bosnia and Herzegovina.
2Faculty of Health, University of Zenica, Bosnia and Herzegovina.
Authors’ contributions
This work was carried out in collaboration between all authors. All authors read and approved the final
manuscript.
Article Information
DOI: 10.9734/BJMMR/2016/23959
Editor(s):
(1) Faris Q. B. Alenzi, Department of Medical Laboratories, College of Applied Medical Sciences Salman bin Abdulaziz
University (Al-Kharj), Saudi Arabia.
Reviewers:
(1) Anonymous, University of Florence, Italy.
(2) Umit Tursen, Mersin University, Turkey.
(3) Joel Schwartz, University of Illinois at Chicago, Chicago, USA.
Complete Peer review History: http://sciencedomain.org/review-history/13289
Received 30th December 2015
Accepted 6th February 2016
Published 14th February 2016
ABSTRACT
Background: Vitiligo is a common skin disorder characterized by macular depigmentation of the
skin. Although the etiopathogenesis of the disease is still unclear, several studies have shown that
within the cascade of pathogenesis of vitiligo, cytokines play an important role.
Objectives: The aim of our study was to evaluate serum concentrations of interleukin- IL-2 (IL-2)
and interleukin-2 soluble receptor (IL-2 sR) in patients with vitiligo and healthy subjects and also to
asses a possible association between these cytokines and duration of the disease.
Study Design: Case control study.
Place of the Study: The study was carried out in University Clinical Center Sarajevo, Department
of Dermatology and Venereology.
Patients and Methods: Twenty one patients (11 female and 10 male; age range 15-53 years) with
vitiligo and 20 healthy controls (10 female and 10 male; age range 17-52) were enrolled in the
study. c The duration of vitiligo ranged from 2 to 252 months. Ten patients (47.62%) had
generalized, and eleven patients (52.38%) had localized vitiligo Serum concentrations of cytokines
Original Research Article
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
2
were measured using enzyme-linked immunoassay techniques.
Results: Both IL-2 (median 22.600 pg/ml, range 20.900-76.100) and IL-2sR (median 76.100 pg/ml,
range 15.700-183.800) in the patient group were significantly higher when compared with that of the
normal controls. When the serum cytokine level in vitiligo group were compared to total disease
duration (Spearman correlation ρ), serum IL-2 was negatively (ρ= -0.000573, P= 0.9980) and IL-2
sR was positively (ρ=0.241, P= 0.2797) correlated with total disease duration, but it is of borderline
significance.
Conclusions: Our results showed hight serum levels of IL-2 and IL2 sR among vitiligo patients
which may highligth a functional role of these cytokines in the pathogenesis of this disease.
Keywords: Vitiligo; serum cytokines; interleukin-2; soluble interleukin-2 receptor.
1. INTRODUCTION
Vitiligo is one of disorders of melanin
pigmentation that affects approximately 0.5-2%
of the population [1]. It is characterized by
macular depigmentation of varying sizes or
shapes with a tendency to progress. Lesions
enlarge centrifugally and can appear on any
body site, including mucous membranes.
Depending on the extent of the lesions, vitiligo
can be classified into two main categories:
generalized and localized. In both types, the
disappearance of functional melanocytes can be
detectable.
The cause of disease is unknown, although there
is evidence for altered immunological processes
in vitiligo, particularly in chronic and progressive
condition [2]. In immune processes, a basic
role is played by cytokines, secreted by
activated cells. They influence other cells via
specific membrane receptors, some of which
have soluble forms, known as soluble receptors
(sR).
Interleukin 2 (IL-2) was discovered in 1976 as a
growth factor for T lymphocytes [3]. Since that
time it has become an important mediator of
immune function though its effects on the growth,
development, and activity of T and B
lymphocytes. Apart from its most important role
to mediate antigen specific T-lymphocyte
proliferation, IL-2 modulates the expression of
interferon-gamma and major histocompatibility
antigens [4,5]. The changes in serum IL-2 levels
were found in many diseases, such as systemic
lupus erythematosus and psoriasis [6]. In some
of these diseases, serum IL-2 concentrations
correlated with activity and intensity of the
disease, and may be used as a prognostic factor.
Because of the central role of IL-2 in immune
response, IL-2 turned out to be very important
molecule for diagnostic and therapeutic
implications.
Interleukin-2 soluble receptor (IL-2 sR) has a
potential role in the modulation of immune
responses by inhibiting IL-2. Clinically, high
levels of IL-2 sR are believed to be associated
with a potent activation of the immune system in
many diseases such as atopic dermatitis,
psoriasis and cutaneous T cell lymphoma [7,8].
Several hypotheses have been proposed to
explain the pathogenesis of vitiligo, and indeed it
is likely that more than one mechanism is
responsible for the clinical manifestations of the
disease [9]. All immune system compartments,
including innate and adaptive immunity have
been implicated in vitiligo development [10].
Recent progress in the understanding of vitiligo
has shown that the regulation of local and
systemic cytokines plays an important role in its
pathogenesis. Although it is well known that
multiple cytokines simultaneously play role in
vitiligo, many authors have measured only one
particular cytokine. Our study has focused only
on IL-2 and IL-2 sR because there are only a few
studies that have measured the serum levels of
these cytokines with controversial results [11-14].
Therefore, the aim of our study was to evaluate
serum concentrations IL-2 and IL- 2 sR in
patients with vitiligo and healthy subjects and
also to asses a possible association between
these cytokines and duration of the disease.
2. MATERIALS AND METHODS
The study included 21 patients with vitiligo, 11
female and 10 male, median age 33.96 (±15.65)
years. Of them, there were 10 (47.62%) patients
with generalized vitiligo and 11 (52.38%) patients
with localized form of disease. A detailed history
and examination were taken in all study subjects,
including patients age, age at onset and duration
of disease. The total disease duration was
defined as the period when the first depigmented
lesion appeared to the day of sample
collection. All patients were examined by the
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
3
dermatologist who made the diagnosis of vitiligo
based on the history, typical clinical features of
depigmented macules and clinical evaluation
including Wood's light examination. In doubtful
cases, skin biopsy was performed (in four
cases). The control group consisted of 20
volunteers, 10 female and 10 male, median age
32.55 (±16.12) years. None of the patients had
used any systemic medications for vitiligo
treatment for at least 3 months before the study.
We excluded the patients with other types of
illnesses, such as autoimmune diseases that
could affect the outcome of the study. Exclusion
criteria consisted of patients who had thyroiditis,
psoriasis, collagenoses, alopecia areata,
diabetes mellitus and depigmenting disorders
other than vitiligo.
All subjects gave their informed consent in
accordance with the requirements of the
Institutional Ethics Committee. The study was
conducted in accordance with the principles of
the Declaration of Helsinki.
2.1 Serum Cytokine Determination
Commercially available kits from R&D Systems
(Minneapolis, USA) were used for the
measurement of serum IL-2 and IL-2 sR levels
by enzyme-linked immunosorbent assay (ELISA)
carried out in accordance with the manufacturer's
instructions.
Briefly, a microplate was coated with a
monoclonal antibody that was specific for the
cytokines, and standards and samples were
pipetted into the wells. After washing, an
enzyme-linked polyclonal antibody that was
specific for the cytokines was added. The
reaction was revealed by addition of the
substrate solution. The colour development was
stopped and the intensity of the colour was
measured at 450 nm with a photometar (Rider
Biotek Elx800).
2.2 Statistical Analysis
Statistical analyses were performed using
MedCalc Statistical Software version 15.2.2.
(MedCalc Software bvba, Ostend, Belgium).
Statistical comparisons were performed using T
test and Mann Whitney U test for independent
samples.The results are expressed as the
median and its range. We used Spearman
correlation coefficient rho for calculate
relationship between duration of disease and
serum levels of cytokines. Data were considered
statistically significance at P<0.01.
3. RESULTS
The study group composed of 21 patients with
vitiligo (11 female and 10 male; the mean age of
the patients was 33.96 years, ranging from 15 to
53 years), and 20 healthy controls (10 female
and 10 male; the mean age 32.55 years, ranging
from 17 to 52 years). There were no significant
difference in age and female/male ratio between
the patients and controls. Dermographic data of
patients and controls are shown in Table 1. The
duration of vitiligo ranged from 2 to 252 months.
Ten patients (47.62%) had generalized, and
eleven patients (52.38%) had localized vitiligo.
Both IL-2 (median 22.600 pg/ml, range 20.900-
76.100) and IL-2sR (median 76.100 pg/ml, range
15.700-183.800) in the patient group were
significantly higher when compared with that of
the normal controls (Table 2).
When the serum cytokine level in vitiligo group
were compared to total disease duration
(Spearman correlation ρ), serum IL-2 was
negatively (ρ= -0.000573, P= .9980) and IL-2 sR
was positively (ρ=0.241, P= .2797) correlated
with total disease duration, but it is of borderline
significance (Table 3).
Table 1. Demographic characteristics of
patients and healthy controls
Vitiligo
group
Control
group
P
Men, n (%) 10 (0,47) 10 (50)
Women, n (%) 11 (0,52) 10 (50)
Age range, years 18-64 17-68
Age, mean years
(SD)
33.96(15.65) 32.55(16.12) 0.889*
* T test
4. DISCUSSION
Although the etiopathogenesis of the disease is
not clear, recent observations support the role of
altered cellular immunity, autoimmunity, and a
role for cytokines in the pathogenesis of vitiligo.
The involvement of activated peripheral and
cutaneous infiltrating T lymphocytes in
melanocytotoxicy has been suggested as an
important patomechanism in vitiligo [15].
Immunohistochemical studies of the perilesional
skin in generalized vitiligo demonstrate the
presence of activated inflammatory T cells,
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
4
Table 2. Cytokines levels in patients and controls
Cytokines Vitiligo (n=21)
(pg/ml)
Controls (n=20)
(pg/ml)
Mann-Whitney U Z P*
IL-2 (med) 22.600 21.300 88.00 3.330 .0009***
Range** 20.900-76.100 10.600-23.800
IL-2R (med) 76.100 44.900 76.00 3.627 .0003***
Range** 15.700-183.800 28.400-71.300
* Mann-Whitney U test, ** Range – min-max values, *** Statistical significance (P<0.01)
mainly CD4+ and CD8+ in the dermal and
epidermal infiltrate [16]. These cells express
activation molecules such as, mayor
histocompatibility complex (MHC) II, CLA antigen
IL-2R (CD25) and interferon-gamma (IFN-γ) [17].
In addition, studies showed that the number of
citotoxic CD8+ T cells was higher in active
disease than in stable disease [18].
Table 3. Relationship between duration of
vitiligo and serum levels of cytokines
(Spearman rank test)
Cytokines rho 95% CI P
IL 2 -0.000573 -0.422-0.421 .9980
IL 2R 0.241 -0.201-0.602 .2797
* Statistical significance (P<0.01)
Many of the actions of immune competent T cells
are primarily mediated through cytokines, and
several reports have shown the presence of
these molecules in the peripheral blood
circulation [19-21] and cutaneous infiltrates in
vitiligo patients [19,22-24].
Cytoknes such as IL-1, IFN-γ or TNF-α are
paracrine inhibitors of melanocytes and can
initiate apoptosis [22]. An imbalance of
keratinocyte –derived cytokines such as IL-6, IL-
1α and TNF-α in the lesional skin has been
demonstrated, which could impair the normal life
and function of melanocytes [23,24]. Higher
levels of the proinflammatory cytokines
interleukin-1α, interleukin-1β, and interleukin-12
measured in epidermis fluid, were presented in
patients whose response to melanocyte
transplantation was unsatisfactory [25]. Wang et
al. [26] reported elevated tisue mRNA levels of
IL-17A in leading edge skin biopsies of
vitiligo patients, as well as IL-17A positive T
cells by immunohistochemistry and
immunofluorescence. In vitro studies confirmed
an increased production of pro-inflammatory
cytokines IL-6 and IL-8 by monocytes of
active patients with vitiligo, which will
affect effector cell migration, effector
target attachment and also cause B cell
activation [27].
IL-2 is a cytokine that seems to play an important
role in vitiligo patients. Wolkenstein et al. [28]
described induction of vitiligo in 4 out 25 patients
treated with IL-2 alone for metastatic melanoma.
This study suggested that vitiligo could be
coused by an autoimmune response of cytotoxic
T lymphocytes against melanocyte antigens. IL-2
is secreted primarily by the T helper
lymphocytes, which in turn stimulate the
production of IL-2R on the T cell surface. The
soluble form of IL-2R (IL-2sR) is then released
into the serum during immune response [29].
Serum levels of IL-2 sR can be used to monitor
in vivo immune activation, and its elevation has
been correlated with T-cell mediated immune
disease [10].
A limited number of studies in the literature have
evaluated the serum levels of IL-2 and IL-2 sR in
patients with vitiligo, and the results were often
contradictory. The results presented in our study
demonstrate that the median serum levels of IL-2
and IL-2 sR were significantly elevated in vitiligo
patients in comparison with healthy subjects. No
significant correlations were found with serum IL-
2 and IL-2sR and disease duration. This reason
why we did not perform the immunochemistry or
HE staining here, is that skin biopsy was
performed in only four cases, in another words,
the biopsy was performed as differential
diagnostic procedure. The purpose was to
determine vitiligo diagnosis in unclear medical
cases.
Recently, increased serum IL-2 [11,30,31] and
IL-2 sR concentrations have also been reported
in peripheral blood [12,32] and tissue [19] but
lower IL-2 sR concentrations [13] were found in
active vitiligo patients.
In contrast to our results, in the study of Tembhre
et al. [14] serum levels of IL-2 in patients with
vitiligo did not differ from the controls. They also
found a significant negative correlation with total
disease duration for IL-2 in active untreated
vitiligo but no correlation was found in untreated
stable vitiligo suggesting the involvement of IL-2
in the induction phase of the disease.
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
5
In many important skin dermatoses the activation
of T lymphocytes is expressed by IL-2 sR and
therefore, its increased serum level in patients
with vitiligo is usually a reliable marker of acute
activation of T cell mediated immunity [19,33].
Yeo et al. [34] showed that IL-2 sR were higher
in vitiligo patients compared with normal controls
in South Korea, and the IL-2 sR levels in patients
with vitiligo of less than 1 year duration was
significantly higher than in patients with vitiligo of
more than 1 year duration. Additionaly, the IL-2
sR levels were not significantly different between
active and inactive group, and there was no
significant differences in IL-2 sR levels when they
were analyzed based on gender of patients, or
age of onset. They concluded that the higher IL-2
sR levels in recent onset group would suggest
that IL-2 sR level might be an acute immunologic
marker in vitiligo patients. Honda et al. reported
that serum IL-2 sR levels were comparable
between localized vitiligo patients and the
controls but were significantly elevated in
patients with generalized vitiligo compared to
controls or to inactive type vitiligo patients in
Japan [35]. After that, Shi et al. demonstrated the
increased serum IL-2 sR levels in vitiligo patients
compared to that of healthy controls, and also
observed increased serum levels of IL-2 sR in
patients with short disease duration, which
further suggest that IL-2 sR levels may represent
a relative early immunologic marker for vitiligo
patients [36].
Also tissue fluids from the margin of
hypopigmented macules, especially in active
disease, seem to contain higher levels of IL-2 sR
than uninvolved skin of the same patients [19]. In
addition, Zailaie observed that treatment of
vitiligo with single dose of oral aspirin for 12
weeks was able to decrease the levels of IL-2 sR
[33]. He concluded that aspirin treatment of
patients with active vitiligo can modulate the
immunologic factors that cause up-regulation of
humoral and cellular immunity involved in
melanocyte cytotoxicity. Of these factors, serum
vitiligo-IgG and IL-2 sR, which are considered as
immunologic markers of vitiligo disease activity.
5. CONCLUSION
Although the initiating event in vitiligo has not yet
been defined, a growing body of evidence
indicates that cytokines may help the
development and the perpetuation of the chronic
inflammatory state. The results presented in our
study demonstrate that the median levels of IL-2
and IL-2 sR were significantly elevated in vitiligo
patients in comparison with healthy subjects. The
imbalance observed in the cytokines examined in
the current study suggest their involvement in the
pathogenesis of vitiligo.
Further studies with a larger sample size are
required to clarify the pathogenic role and clinical
significance of IL-2 and its soluble receptor, and
these findings may provide important clues to
assist in the development of new therapeutic
strategies for patients with vitiligo.
CONSENT
All authors declare that written informed consent
was obtained from the patients for publication of
this research article.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
REFERENCES
1. Bystrin JC. Serum autoantibodies in vitiligo
patients. Clin Dermatol. 1989;7(2):136-45.
2. Laddha NC, Dwivedi M, Mansuri MS, Gani
AR, Ansarullah M, Ramachandran AV, et
al. Vitiligo: Interplay between oxidative
stress and immune system. Experimental
Dermatology. 2013;22(4):245-50.
3. Morgan DA, Ruscetti FW, Gallo R.
Selective in vitro growth of T lymphocytes
from normal human bone marrows.
Science. 1976;193(4257):1007-8.
4. Reem GH, Yeh NH. Interleukin 2 regulates
expression of its receptor and synthesis of
gamma interferon by human T
lymphocytes. Science. 1984;225(4660):
429-30.
5. Liao W, Lin JX, Leonard WJ. IL-2 family
cytokines: New insights into the Complex
roles of IL-2 as a broad regulator of T
helper cell differentiation. Curr Opin
Immunol. 2011;23(5):596-604.
6. Roussaki-Schulze AV, Kouskoukis C,
Petinaki E, Klimi E, Zafiriou E, Galanos A,
et al. Evaluation of cytokine serum levels
in patients with plaque-type psoriasis. Int J
Clin Pharmacol Res. 2005;25(4):169-73.
7. Elkayam O, Yaron I, Shirazi I, Jaron M,
Caspi D. Serum levels of IL-10, IL-6, IL-
1ra, and IL-2R in patients with psoriatic
arthritis. Rheumatol Int. 2000;19(3):101-5.
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
6
8. Furue M, Sugiyama H, Tsukamoto K,
Ohtake N, Tamaki K. Serum soluble IL-2
receptor (sIL-2R) and Eosinophil Cationic
Protein (ECP) levels in atopic dermatitis. J
Dermatol Sci. 1994;7(2):89-95.
9. Le Poole IC, Das PK, Van den Wijngaard
RM, Bos JD, Westerhof W. Review of the
etiopathomechanism of vitiligo: A
convergence theory. Exp Dermatol. 1993;
2(4):145-53.
10. Rezaei N, Gavalas NG, Weetman AP,
Kemp EH. Autoimmunity as an aetiological
factor in vitiligo. JEADV. 2007;21(7):865-
76.
11. Singh S, Singh U, Pandey SS. Serum
concentration of IL-6, IL-2, TNF-α, and
IFN-γ in vitiligo patients. Indian J Dermatol.
2012;57(1):12-4.
12. Galadari I. Serum levels of the soluble
interleukin-2 receptor in vitiligo patients in
UAE. Eur Ann Allergy Clin Immunol. 2005;
37(3):109-11.
13. Franczuk A, Szepietowski JC, Noworolska
A. Serum concentrations of interleukin-2
soluble receptor (IL-2 sR) in patients with
vitiligo: Relationship with type and extent
of the disease. Acta Dermatovenerol
Croat. 2004;12(2):71-6.
14. Tembhre MK, Sharma VK, Sharma A,
Chattopadhyay P, Gupta S. T helper and
regulatory T cell cytokine profile in active,
stable and narrow band ultraviolet B
treated generalized vitiligo. Clinica Chimica
Acta. 2013;424(23):27-32.
15. Ongenae K, Van Geel N, Naeyaert JM.
Evidence for an autoimmune pathogenesis
of vitiligo. Pigment Cell Res. 2003;16(6):
90-100.
16. Al Badri AM, Todd PM, Garoch J,
Gudgeon JE, Stewart DG, Goudie RB. An
immunohistological study of cutaneous
lymphocytes in vitiligo. J Pathol. 1993;
170(2):149-55.
17. van den Wijngaard R, Wankovitcz-
Kalinska A, Le Poole C, Tigges B,
Westerhof W, Das P. Local immune
response in skin of generalized vitiligo
patients. Destruction of melanocytes is
associated with the prominent presence of
CLA+ T cells at perilesional site. Lab
Invest. 2000;80(8):1299-1309.
18. Rao A, Gupta S, Dinda AK, Sharma A,
Sharma VK, Kumar G et al. Study of
clinical, biochemical and immunological
factors determining stability of disease in
patients with generalized vitiligo
undergoing melanocyte transplantation. Br
J Dermatol. 2012;166(6):1230-1236.
19. Caixia T, Hongwen F, Xiran L. Levels of
soluble interleukin-2 receptor in the sera
and skin tisue fluids of patients with vitiligo.
J Dermatol Sci. 1999;21(1):59-62.
20. Ala Y, Pasha MK, Rao RN, Komaravalli
PL, Jahan P. Association of IFN-γ:IL-10
cytokine ratio with nonsegmental vitiligo
pathogenesis. Autoimmune Dis. 2015;
423490.
21. Osman AM, Mukhtar MM, Bakheit KH,
Hamdan HZ. Plasma levels of interleukin-
17, interleukin-23, and transforming growth
factor-β in Sudanese patients with vitiligo:
A case-control study. Indian J Dermatol.
20015;60(6):635.
22. Huang CL, Nordlund JJ, Boissy R. Vitiligo:
A manifestation of apoptosis? Am J Clin
Dermatol. 2002;3(5):301-8.
23. Moretti S, Spallanzani A, Amato L,
Hautmann G, Gallerani I, Fabiani M,
Fabbri P. New insights into the
pathogenesis ogf vitiligo: Imbalance of
epidermal cytokines at sites of lesions.
Pigment Cell Res. 2002;15(2):87-92.
24. Moretti S, Fabbri P, Baroni G, Berti S, Bani
D, Berti E, et al. Keratinocyte dysfunction
in vitiligo epidermis: Cytokine
microenvironment and correlation to
keratinocyte apoptosis. Histol Histopathol.
2009;24(7):849-57.
25. Zhou MN, Zhang ZQ, Wu JL, Lin FQ, Fu
LF, Wang SQ, et al. Dermal mesenchymal
stem cells (DMSCs) inhibit skin-homing
CD8+ T cell activity, a determining factor of
vitiligo patients' autologous melanocytes
transplantation efficiency. PLoS One.
2013;8(4):e60254.
26. Wang CQ, Cruz-Inigo AE, Fuentes-
Duculan J, Moussai D, Gulati N, Sullivan-
Whalen M, et al. Th17 cells and activated
dendritic cells are increased in vitiligo
lesions. PLoS One. 2011;6(4):e18907.
27. Yu HS, Chang KL, Yu CL, Li HF, Wu ML,
Wu CS. Alterations in IL-6, IL-8, GM-CSF,
TNF-alpha, and IFN-gamma release by
peripheral mononuclear cells in patients
with active vitiligo. J Invest Dermatol.
1997;108(4):527-9.
28. Wolkenstein P, Chosidow O, Guillaume
JC, Wechsler J, Avril M, Revuz J. Vitiligolike
lesions in melanoma treated with
interleukin-2: 4 cases. Ann Dermatol
Venereol. 1992;119(11):907-9.
Kasumagic-Halilovic et al.; BJMMR, 13(10): 1-7, 2016; Article no.BJMMR.23959
7
29. Gaulton GN, Williamson P. Interleukin-2
and the interleukin-2 receptor complex.
Chem Immunol. 1994;59:91-114.
30. Khan R, Gupta S, Sharma A.
Circulatory levels of T-cell cytokines
(interleukin [IL]-2, IL-4, IL-17, and
transforming growth factor-β) in patients
with vitiligo. J Am Acad Dermatol.
2012;66(3):510-11.
31. Tsiskarishvili NV, Katsitadze A,
Tsiskarishvili NI, Chitanava L. Perculiarities
of cytokine status in patients with vitiligo
and stress in anamnesis. Georgian Med
News. 2014;235:45-8.
32. Tu CX, Fu HW, Lin XR. Levels of soluble
interleukin-2 receptor in the sera and skin
fluids of patients with vitiligo. J Dermatol
Sci. 1999;21(1):59-62.
33. Zailaie MZ. Aspirin reduced serum antimelanocyte
antibodies and soluble
interleukin-2 receptors in vitiligo patients.
Sauudi Med J. 2005;26(7):1085-91.
34. Yeo UC, Yang YS, Park KB, Sung HT,
Jung SY, Lee ES et al. Serum
concentration of the soluble interleukin-2
receptors in vitiligo patients. J Dermatol
Sci. 1999;19(3):182-8.
35. Honda Y, Okubo Y, Koga M. Relationship
between levels of soluble interleukin-2
receptors and the types and activity of
vitiligo. J Dermatol. 1997;24(9):561-3.
36. Shi YL, Li K, Hamzavi I, Lim HW, Zhan L,
Mi QS. Elevated circulating soluble
interleukin-2 receptor in patients with nonsegmental
vitiligo in North America. J
Dermatol Sci. 2013;71(3):212-4.
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© 2016 Kasumagic-Halilovic et al.; This is an Open Access article distributed under the terms of the Creative Commons
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