Biosci. Biotech. Res. Comm. 10(3): 514-517 (2017)
Interleukin-17 concentration as a biomarker in diagnosis
of exudative pleural effusion compared with benign
pleural effusion
Ali Arian Nia*
and Saeid Mehrabi
Clinical Research Development Unit (CRDU) Golestan University of Medical Sciences Gorgan Iran
MD Golestan University of Medical Sciences Gorgan Iran
Pleural effusion is one of signs and complications resulting from malignant disease such as lung and breast cancer, and
also tuberculosis and infective lung disease by cytological analysis of pleural  uid we can use of tumor marker and other
biomarkers to better diagnose malignant pleural this study we examined the concentration of interleukin-17 in
pleural  uid with causes of exudative pleural effusion in the patients referred to hospital of 2015-2016.This is a descriptive-
analytical and case-control study and 130 patients with exudative pleural effusion were enrolled in the study after an
informed consent samples collected from the patients divide into two main group including 88 patients with malignant
pleural effusion and 42 patient with benign effusion. in the next step by using of the same previous pleural  uid samples,
the concentration of interleukin-17 was measured with ELISA by speci c kit after entering to computer through SPSS-
18 statistical software, description of data was done into frequency and percentage.Interleukin-17 concentration was
(69.73±64.58) in patients with malignant causes and (55.32±43.60) in benign causes.The results showed that this differ-
ent was statistically signi cant (P=0.02) and interleukin -17 rate, is higher in the malignant pleural effusion.According
to higher levels of interleukin-17 in malignant pleural effusion maybe we can achieve important result in differentiating
between malignant and non-malignant pleural exudate, without the need for invasive procedures, by putting together the
clinical symptoms, the interleukin-17 concentration in pleural  uid and pleural  uid cytology results.
*Corresponding Author:
Received 27
Nov, 2017
Accepted after revision 26
Sep, 2017
BBRC Print ISSN: 0974-6455
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Online Contents Available at:
DOI: 10.21786/bbrc/10.3/26
Ali Arian Nia and Saeid Mehrabi
Pleural effusion is an excessive accumulation of  uid
in the pleural space, which affects annually about one
million people around the world. There are a range of
causes for the disease; benign diseases such as infec-
tions, heart and liver failures, rheumatic diseases and
drugs on the one hand and fatal cancers of lung and
other visceral organs on the other hand are placed in
this spectrum (Esther et al 1997).
Plain chest pleurography is a simple diagnostic meas-
ure to detect pleural effusion, which appears as  at-
tening and displacement between costophrenic angles.
With the presence of less  uid or abnormal localiza-
tion, ultrasound or CT scan can be used to conduct pleu-
ral tap (Heffner et al 1997, Light et al 1972, Ryland et
al1998). Cytologic analysis of pleural  uid is the most
common method for diagnosis of malignancy; while the
speci city of cytologic  ndings is 100%, unfortunately
only about 60% of malignant effusions can be detected
through this technique (Alema’n et al 2010). For undi-
agnosed exudative effusions with suspicion of malig-
nancy but negative cytology, more invasive approaches
are necessary (Hooper et al 2010 Chun Hua et al., 2017).
Closed pleural biopsy has less additional diagnostic
value and thoracoscopy is the preferred method, since
it is diagnostic in 90% of patients (Light 2006, Roberts
2010 and Neragi-Miandoab 2006). However, there is no
possibility of access to this invasive procedure in all
centers. Many investigations have assessed the ability
of tumor markers and other biomarkers to improve the
diagnosis of MPE (Botana-Rial et al 2011, Kremer et al
2010).The combined use of different markers has also
been proposed in some studies ( Kremer et al 2010, 2013).
Unfortunately, none of these markers has shown the
sensitivity and speci city enough to select as a diagnos-
tic marker of MPE (Hooper et al 2010). In a study, a type
of chemical safety approach has been used to search
for non-invasive markers of lung cancer in PE (Porcel
et al 2004). In this regard, several chemical biomark-
ers of in ammation were found that were differentially
expressed in MPE vs. BPE. Among these biomarkers,
IL-17 and CEA were expressed at higher quantities in
MPE than BPE. Interleukin 17 is a potential in amma-
tory cytokine produced by Th17 cells; it is expected to
be used as a marker for the diagnosis of pleural effusion.
The aim of this study is to determine the concentra-
tion of IL-17 in pleural  uid to facilitate differentiation
between MPE and BPE.
The Deputy of Science and Technology of Golestan Uni-
versity of Medical Sciences and Research Ethics Com-
mittee approved study design and implementation pro-
tocol. All actions taken, had no physical, psychological
or  nancial losses for the participants in the research.
This descriptive and analytical study was performed on
130 patients with exudative pleural effusion who were
admitted to Shahid Sayyad Shirazi Teaching Hospital
in Gorgan during 2015-2016, and enrolled in the study
after obtaining informed consent.Routine diagnostic
procedures such as X-ray, CT scan and ultrasound, if
necessary, were performed for all patients before start-
ing the study. After history taking and exact physical
examination, thoracentesis was carried out to prepare
pleural  uid samples that were frozen at -20°C after cen-
trifugation for 15 min.
The samples were analyzed for biochemical proper-
ties, pH, glucose and proteins; accordingly, exudative
pleural effusion was differentiated from transudative
type and patients with transudative pleural effusion
were excluded from the study. Malignancy of pleural
effusion was diagnosed according to our and previous
studies using VATS technique; such that, after insert-
ing VATS instruments through 1 to 2 incisions and after
viewing the parietal and visceral pleura as well as evi-
dence of metastases, biopsy was performed from the
parietal pleura and pleural  uid for cytology testing.
The samples were sent to the pathology laboratory for
detecting malignancy and its type.
In terms of etiology and based on the  ndings of the
gold standard of pleural  uid analysis (microbiology
and cytology testing, including cell differential count),
exudative pleural effusion were classi ed into two main
MPE and BPE groups. According to previous studies,
since between 40 and 50 percent of the cases showed
malignant exudative pleural effusion, so the samples
were divided almost with the same proportion. At a later
stage, by using the same previous pleural  uid samples,
the IL-17 levels were measured via ELISA kit accord-
ing to the manufacturer’s protocol and the samples were
stored at -80°C until testing.Having pleural effusion dis-
ease was inclusion criterion. Exclusion criteria included
transudative pleural effusion, diabetes, autoimmune dis-
eases and rheumatic diseases.
Data were analyzed using statistical SPSS V.18 soft-
ware. Normal distribution and data homogeneity were
assessed using the Kolmogorov-Smirnov test.
In addition, the mean IL-17 level was compared
between the two groups using independent t-test. Mann-
Whitney test was applied for normal distribution of IL-17
concentration. Signi cance level of the tests was 0.05.
After examining, 130 patients were divided into two
groups of malignant pleural effusion (n=88, 67.7%) and
Ali Arian Nia and Saeid Mehrabi
benign pleural effusion (n=42, 32.3%) with a mean age
of 57 and 59 years respectively. There was no statistically
signi cant difference between IL-17 level and age of the
patients. The patients in MPE group included 44 males
(50%) and 44 females (50%), but the patients in BPE group
consisted of 26 males (61.9%) and 16 females (38.1%).
In the MPE and BPE groups, 41 and 21 people were
smokers respectively. Among the patients in MPE group,
22 (25%) had primary lung cancer, 31 (35.2%) secondary
breast cancer, 11 (12.5%) secondary esophageal cancer,
11 (12.5%) metastatic cancer and 13 (14.77 %) secondary
stomach cancer.
The IL-17 level was 36.43±56.719 in males and
74.838±76.42 in females; and as a result of statistical
analysis, no signi cant difference was observed for IL-17
levels in pleural  uid between males and female. Analysis
of the mean pleural  uid protein levels was respectively
4373.8± 419.3 mg and 4411.7 ± 493 mg in the patients of
MPE and BPE groups. There was a correlation between
IL-17 and pleural  uid protein levels, but it was not
statistically signi cant (r = 0.15). The mean IL-17 level
was compared in smokers and nonsmokers, and statisti-
cal analysis showed no signi cant difference (P = 0.35).
The results showed that 66 patients (50.8%) had a history
of previous malignancy; 31 (46.97%) secondary to breast
cancer, 11 (16.67%) secondary to esophageal cancer, 11
(16.67%) secondary to metastasis due to other causes and
13 (19.7%) secondary to stomach cancer had experienced
MPE, and the mean IL-17 level was 63.9±36.6 in these
subjects. In people who had no history of previous malig-
nancy, including 22 (34.38%) with primary lung cancer
and 42 (65.63%) with TB (totally 64 patients, 49.2%), the
mean IL-17 level was 66.2 ± 75.5 in these people. Con-
sidering the higher mean IL-17 level in the group with
no history of previous malignancy compared with the
rst group as well as P= 0.001, no statistically signi -
cant difference was observed for IL-17 levels between the
two groups. The IL-17 level in pleural  uid of patients
with MPE and BPE was respectively 69.73± 64.58 and
55.32±43.60; there was a statistically signi cant differ-
ence between the two groups (P = 0.02).
Differentiating between benign pleural effusion (BPE)
and malignant pleural effusion (MPE) has remained
controversial as a diagnostic issue. The majority of
malignant pleural effusion (90% to 97%) is exudative
type that occurs because of pleural membrane damage
(Esther et al 1997). MPE can be seen as a complication
in most malignancies, particularly in breast and lung
cancer, while lung infections and tuberculosis cause the
development of BPE.The gold standard for diagnosis of
malignant pleural effusion is clinically the presence of
malignant cells in pleural cells. Dif culty in differentiat-
ing between malignant and benign is the negative result
of malignant cells in pleural  uid cytology. In these cir-
cumstances, differentiation from benign is problematic
and the need for invasive measures such as thoracentesis
is essential for the patient.
Closed pleural biopsy has less additional diagnostic
value and thoracoscopy is the preferred method, since
it is diagnostic in 90% of patients. However, there is
no possibility of access to this invasive procedure in all
centers. According to this issue, 130 patients with exu-
dative pleural effusions were examined in this study. In
the present study, 88 patients with malignant pleural
effusion were compared with 42 patients with benign
pleural effusion in terms of pleural  uid levels of IL-17.
The patients were also evaluated for age, gender, his-
tory of previous cancer, smoking and pleural  uid pro-
tein levels. The mean age of subjects was close to each
other in two age groups and no signi cant difference
was found between the two groups. In addition, there
was no statistically signi cant difference between IL-17
level and age of the patients.
In 2014, Chun Hua et al. examined a new biomark-
ers of interleukin 17 among 123 patients with exuda-
tive pleural effusion to determine the causes of pleural
effusion. They showed that IL-17 level was signi cantly
higher in MPE group compared with BPE group, similar
to our results, and also stated that IL-17 can be used as
a biomarker to differentiate MPE from BPE.
Since only one study has so far examined the level
of IL-17 in pleural  uid, in addition to our study; so in
the following discussion, we will consider similar studies
closer to the present study, (Chun Hua et al., 2017).
Wang et al. in 2013 examined the levels of superox-
ide dismutase (SOD) in TPE and MPE, which was mark-
edly higher in the TPE than the MPE. The results showed
that SOD is not a suitable biomarker for these two types
of pleural effusion (Xin-Feng Wang et al, 2013) In 2014,
Chun Hua et al. examined serum levels of IL-17 in 128
patients with Non-small cell lung cancer (NSCLC). The
results showed that higher levels of IL-17 in NSCLC group
compared with the control group, which can be applied as
diagnostic and prognostic value in patients with NSCLC.
Many studies have been conducted in the  eld of
diagnostic value of cytology and the diagnostic value
for diagnosing malignancies have been reported up to
70% in Iran. More invasive procedures such as biopsy,
thoracoscopy or thoracotomy despite high sensitivity
are not accepted through patients and physicians for
diagnosis of tuberculosis and malignancies.
Therefore, researches in recent decades have led to
nd markers in pleural effusion and blood plasma to dif-
ferentiate between tuberculosis and malignancies with-
out invasion and with high-value and effectiveness of
diagnosis and differentiation.
So far, only one study has examined the level of
IL-17 in pleural effusion and high sensitivity has been
Ali Arian Nia and Saeid Mehrabi
able to differentiate MPE than BPE. Like what mentioned
above, other studies have been done on other biomark-
ers that some of them have been useful for the study. In
our study, according to the signi cant differences for
IL-17 levels in the two groups, its usability can be seen
to differentiate between MPE and BPE. In addition, since
the patients with primary lung cancer were in the group
with no history of previous malignancy and the mean
IL-17 was higher in these patients than in patients with
secondary cancer as well as than TB, so signi cant dif-
ference was found between the two groups regarding
history of previous cancer, though given limited studies
done in this area and the lack of de ned cut-off points,
it de nitely cannot be used as the only reference and
diagnostic methods. Nevertheless, due to the apparent
signi cant difference between the two groups, there is
the possibility of using IL-17 beside other methods for
differentiating malignant from benign diseases.
The results obtained from the present study demon-
strated that age, gender, smoking, history of previous
cancer and pleural effusion protein levels have no sig-
ni cant effect on IL-17 level. The IL-17 level was signif-
icantly higher in pleural effusion caused by malignant
diseases than in exudative pleural effusion caused by
benign diseases, especially tuberculosis.
Since the differentiation between malignant pleural
effusion and benign pleural effusion, especially tuber-
culosis, sometimes needs to invasive procedures such as
pleural biopsy or thoracoscopy, so it can be concluded
that the IL-17 level regarding the signi cant difference
can be used as a diagnostic approach in differentiating
between the two types of pleural effusion.
It is recommended that the similar study should be
conducted in different centers with larger sample size, as
well as a variety of malignant and benign diseases can
be studied separately.
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