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Maternal and umbilical serum levels of interleukin-6, interleukin-8, and
tumor necrosis factor-ain normal pregnancies and in pregnancies
complicated by preeclampsia
MI
GRACI TOSUN
1
, HANDAN CELIK
1
, BAHATTIN AVCI
2
, ERHAN YAVUZ
1
,
TAYFUN ALPER
1
, & ERDAL MALATYALIO
GLU
1
1
Department of Obstetrics and Gynecology and
2
Department of Biochemistry, Ondokuz Mayis University, Samsun, Turkey
(Received 1 November 2009; accepted 11 March 2010)
Abstract
Objectives. The aim of this study was to investigate the relationship of maternal and umbilical cord interleukin-6 (IL-6),
interleukin-8 (IL-8), tumor necrosis factor-a(TNF-a) serum levels with the existence and severity of preeclampsia. A
particular objective was the comparison of normal umbilical serum levels to preeclamptic values.
Materials and Methods. The study group consisted of 24 patients with third trimester singleton pregnancies complicated by
preeclampsia (15 severe and 9 mild preeclampsia). The gestational age-matched 19 healthy pregnant women were compared
by study group. Maternal and umbilical serum IL-6, IL-8, and TNF-awere calculated by using enzyme-linked
immunosorbent assay.
Results. Significantly increased maternal and umbilical serum levels of IL-6, IL-8, and TNF-awere found in preeclamptic
patient group in comparison with the control group. Maternal serum IL-8 and TNF-aconcentration were significantly
higher in patients with severe preeclampsia than in mild preeclampsia. Increased umbilical serum levels of IL-6 and IL-8
were found in severe preeclampsia than in mild preeclampsia. There were significantly higher levels of maternal serum IL-8
and TNF-ain patients with preeclampsia with IUGR than in patients with preeclampsia with normal fetal growth.
Conclusion. Our findings suggest that increased concentrations of IL-6, IL-8, and TNF-ain the maternal and umbilical
serum play a significant role in pathogenesis of preeclampsia. Alterations in maternal and umbilical serum levels of IL-6,
IL-8, and TNF-amay also play role in preeclampsia complicated by intrauterine growth retardation. These associations may
offer insight into the etiology and pathogenesis of preeclampsia.
Keywords: Interleukin-8, interleukin-6, tumor necrosis factor-a, preeclampsia
Introduction
Preeclampsia is a relatively common gestatitional
disorder affecting about 2.5–5% pregnancies. It
occurs in the second half of pregnancy and is
characterized by proteinuria and hypertension [1].
Preeclampsia is still one of the leading causes for
maternal and fetal mortality and morbidity. Although
placental ischemia and endothelial damage have
been reported as the key factors in preeclampsia,
the exact pathological process has not been identi-
fied, yet [1,2].
In a normal pregnancy, mild inflammatory re-
sponse including increased release of inflammatory
cytokines, activation of granulocytes and comple-
ment system is present, but in preeclampsia there is
excessive maternal inflammatory response, possibly
against foreign fetal antigens resulting abnormal
trophoblast invasion [3].
In a study, myometrial vessels of uncomplicated
pregnant women were incubated with the plasma
obtained from both preeclamptic and normal preg-
nant women. In plasma of preeclamptic women,
endothelium-dependent relaxation was significantly
reduced. So it was thought that altered cytokines in
plasma may be one of the causative factors for
abnormal placentation and endothelial dysfunction
[4].
Interleukin-6 (IL-6) is produced by human tro-
phoblasts. It increases trophoblastic proliferation,
Correspondence: Handan Celik, Department of Obstetrics and Gynecology, Ondokuz Mayis University, Samsun, Turkey. E-mail: drhandancelik@
hotmail.com
The Journal of Maternal-Fetal and Neonatal Medicine, August 2010; 23(8): 880–886
ISSN 1476-7058 print/ISSN 1476-4954 online Ó2010 Informa UK Ltd.
DOI: 10.3109/14767051003774942
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invasion, and differentiation. It is a multifunctional
cytokine that regulates also immune response,
hematopoiesis, acute phase reactions, and inflamma-
tion [5–7].
Interleukin-8 (IL-8) is a major neutrophil che-
moattractant. It has been found in endothelial cells
and regulates endothelial cell proliferation, angio-
genesis, and tumor growth and participates in graft
rejection and placental infection [8–10].
Tumor necrosis factor-a(TNF-a) is a polypeptide
cytokine produced by monocytes and macrophages.
TNF-ais a potent immune modulator also. It acts in
inflammation, endothelial cell activation, regulation
of metabolic activities of tissues, shock, and death. It
circulates throughout the body responding the
stimuli, like tissue injury or infectious agents by
activating neutrophils and changing the endothelial
cell functions [11,12].
On the basis of these facts, IL-6, IL-8, and TNF-a
may be involved in the pathophysiological processes
causing preeclampsia. Evaluation of abnormal in-
flammatory response and defective trophoblast inva-
sion in preeclampsia may improve the understanding
of pathophysiological mechanisms, prevention, and
treatment of preeclampsia.
So we aimed to compare serum levels of IL-6, IL-
8, and TNF-ain maternal and umbilical cord of
healthy pregnant women to those measured in the
presence of preeclampsia. For the case of a possible
relationship, an investigation of correlation with the
severity of disease was also premeditated.
Materials and methods
All samples were obtained from patients and healthy
pregnant women admitted to Ondokuz Mayıs Uni-
versity, Obstetrics and Gynecology Department.
Ethical approval was received from ethics committee
of the same University and all participants gave
informed signed consent.
Nineteen normotensive pregnant women were
age-, parity-, and gestational age- matched with 24
women with preeclampsia.
Mean gestational age of patients was 37, 74 +1.43
weeks (range: 37–40 weeks). Gestational age differ-
ence between the controls and cases was 2 weeks.
Mean maternal age and mean parity was 28.48 +
5.42 years (range: 19–41 years) and 1.06 +1.14
(range: 0–5), respectively. Maternal age difference
within 4 years and parity within 2 were matched with
each other.
Study group was further classified as mild and
severe preeclampsia according to disease severity.
Preeclampsia was defined as if the blood pressure
diagnosed after 20 weeks of pregnancy was 140/
90 mmHg or greater 6 h apart with proteinuria of
300 mg/day or one dipstick measurement of þ1
according to the Committee of Terminology of
American College of Obstetricians and Gynecolo-
gists definition. Preeclampsia was categorized as
severe if the systemic blood pressure was 160/
110 mmHg or more on two occasion 6 h apart with
severe daily (45 g/day) or with one dipstick mea-
surement of þ3orþ4 proteinu¨ ria. Presence of visual
disturbances, upper abdominal pain, convulsion,
oliguria, headache, elevated serum liver enzymes or
serum creatinine, thrombocytopenia was other evi-
dences of severe preeclampsia. Women who met the
preeclampsia criteria but not severe preeclampsia
were classified as mild preeclampsia. Initially all the
candidates were evaluated by measuring the blood
pressure 6 h apart, by proteinuria with 24 h mea-
surement or with one dipstick measurement of þ3or
þ4 proteinuria (in some of the patients with severe
preeclampsia in whom the delivery was planned
before 24 h) as well as by clinical and biochemical
tests. In the first 24-h of hospitalization period, the
patients were assigned to the severe or mild
preeclampsia group, according to the result of these
parameters. Patients classified as severe preeclampsia
were given an intravenous infusion of MgSO
4
with
2 g per hour after a loading intravenous dose of 6 g
MgSO
4
.
All healthy control subjects presented with single-
ton uncomplicated pregnancies without evidence of
hypertension or proteinuria and gave birth to healthy
neonates of appropriate size for gestational age.
Intrauterine growth retardation (IUGR) was de-
fined as a birth weight below the 10th percentile for
gestational age. Patients with preeclampsia were
further divided into two groups according to the
presence or absence of growth retardation.
Gestational age of all pregnant women participated
in the study was 37 weeks. The serum samples
were taken from the patients before the cesarean
delivery and from the umbilical vein before the
delivery of placenta by cesarean section. Pregnancies
with chronic hypertension, diabetes mellitus, kidney
diseases, fetal chromosomal or structural abnormal-
ities, polyhydramnios, and multiple pregnancies were
excluded from the study. The patients in active phase
of labor, premature rupture of membranes, clinical
chorioamnionitis, and maternal autoimmune or
infectious diseases recognized in pregnancy and the
other factors (multiple gestation, fetal anomaly,
intrauterine fetal death, and fetal distress) that may
affect the IL level in serum were also excluded from
the study. All participants underwent cesarean
section. As active labor may effects serum levels of
interleukins, women with active labor or delivering
vaginally were excluded from the study. Active phase
of labor was defined as a faster rate of cervical
dilatation which begins with 2–4 cm dilatation of
cervix.
Role of interleukins in preeclampsia 881
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Preeclampsia, previous cesarean section, abnormal
fetal position, cephalopelvic disproportion were the
indications for cesarean delivery.
Ten milliliters of blood were taken by venipunc-
ture from each woman before the cesarean delivery
and from umbilical vein of placental cord just after
the delivery of baby. All samples were collected in
sterile tubes and stood at room temperature at least
30 min for clotting and then centrifuged at 4500gfor
10 min. Serum was separated and stored 7808C
until assay. Maternal and umbilical serum IL-6,
IL-8, TNF-aconcentrations were assayed using
commercially available kits according to the manu-
facturer’s instructions. The concentrations of IL-6
and TNF-ain the serum were assayed using
commercially available enzyme-linked immunosor-
bant assay (ELISA) kits (BioSource International,
Camarillo, CA), and the concentrations of IL-8 in
the serum were assayed using Ray-bio ELISA kit
(Ray-Bio Tech, Norcross, GA). Lower detection
limits were 2, 1, and 0.7 pg/ml for IL-6, IL-8 and
TNF-a, respectively. Interassay coefficient of varia-
tion (CV) % and intraassay CV % for IL-6, IL-8, and
TNF-awere 4.4%, 512%, 3.3% and 4.2%, 510%,
6.3% respectively. All assays were conducted accord-
ing to the manufacturer’s instructions. The samples,
which have shown higher concentrations, were
diluted and measured in triplicate.
Statistical analyses were done with NCSS 2007
and PASS 2008 Statistical Software (Utah, USA).
Data were expressed as mean +standard deviation.
Groups were compared by using Student’s t-test,
chi-square test as appropriate. In the absence of
normal distribution and nonparametric data Mann–
Whitney U-test was used (Mann–Whitney U-test
was used to determine significant differences in
biochemical parameters between pregnant women
with severe preeclampsia and mild preeclampsia and
between pregnant women with preeclampsia and
controls). Pvalues 50.05 was considered statistical
significance.
Results
A total of 26 women with preeclampsia and 21
normal pregnant women were enrolled into the
study. Two patients from the preeclampsia group
(one patient with fetal anomaly and one patient with
polyhidramnios) and two patients from the control
group (both with a gestational age of lower than 37
weeks) were excluded from the study. The remaining
24 women with preeclampsia and 19 normal
pregnant women were studied. Clinical character-
istics of patients are shown in Table I. There were no
statistically significant differences in maternal age
gravidity, parity, and body mass index between
normal pregnancy and those with preeclampsia.
None of the subjects were smokers in both study
and control groups. The mean systolic and the mean
diastolic blood pressure values were significantly
higher in preeclampsia than normal pregnancy
(P50.05). Mean gestational age at the time of
delivery (37.12 +1.45 weeks vs. 38.52 +0.96
weeks) and mean birth weight of infants (2530 +
425 g vs. 3310 +450 g) were significantly lower in
preeclampsia than in normal control subjects.
The mean concentrations of IL-6, IL-8, TNF-ain
maternal and umbilical cord serum of normal
pregnancy group and the preeclamptic group were
shown in Table II. Serum concentrations of IL-6,
IL-8, and TNF-awere significantly different among
the groups. Increased maternal and umbilical serum
levels of IL-6, IL-8, and TNF-awere found in
preeclampsia group in comparison with the control
group. The maternal serum concentrations of IL-6 in
preeclampsia and in control groups were 57.93 pg/
ml (range: 30.19–669.79 pg/ml) and 13.57 pg/ml
(range: 5.45–476.45 pg/ml), respectively (P50.01).
The maternal serum levels of IL-8 were 403.86 pg/
ml (range: 140.40–1056.55 pg/ml) in preeclampsia
and 88.70 pg/ml (range: 74.29–774.71) in control
group. The maternal serum values of TNF-awere
14.93 pg/ml (range: 4.06–30.67 pg/ml) in pree-
clampsia and 4.5 pg/ml (range: 2.32–30.67 pg/ml)
in control group. These differences were statistically
significant (P50.01).
There were higher levels of IL-6 in the um-
bilical serum in preeclamptic patients than in
controls (114.51 pg/ml (range: 43.57–712.89 pg/
ml) and 23.72 pg/ml (range: 7.48–422.62 pg/ml)
Table I. Clinical findings of patients.
Mean +SD
P
Preeclampsia
(n¼24)
Normal
pregnancy
(n¼19)
Maternal
age (years)
28.5 +5.83 28.47 +5.01 0.988
Parity 1.67 +1.31 0.95 +0.91 0.816
Body mass
index (BMI)
(kg/m
2
)
28.9 +6.4 27.4 +5.6 0.04
Gestational
age at delivery
(weeks)
37.12 +1.45 38.52 +0.96 0.001**
Birth weight
of infant (g)
2530 +425 3310 +450 0.001**
Systolic blood
pressure
(mmHg)
162 +25 118 +13 0.001**
Diastolic blood
pressure
(mmHg)
120 +13 73 +5 0.001**
*P50.05; **P50.01.
882 M. Tosun et al.
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respectively) (P50.01). Umbilical serum levels of
IL-8 and TNF-awere significantly higher in pre-
eclampsia than in normal pregnant women also
(IL-8 umbilical serum levels: 254.58 pg/ml (range:
140.73–6707 pg/ml) in preeclampsia and 135.02
pg/ml (range: 135.02–940.69 pg/ml) in control
group (P50.01)) TNF-aumbilical serum levels:
15.95 pg/ml (range: 5.66–19.78 pg/ml) in pree-
clampsia and 9.18 pg/ml (range: 4.06–18.27 pg/ml)
in control group (P50.05).
The pregnant women with preeclampsia were
further divided into the two groups according to
the disease severity. There were 15 severe pree-
clampsia and nine mild preeclampsia. The maternal
and umbilical serum levels of IL-6, IL-8, and TNF-a
in mild and severe preeclampsia are shown in
Table III.
Maternal serum levels of IL-8 and TNF-awere
significantly related with the disease severity. In
severe preeclampsia, IL-8 and TNF-amaternal
serum levels were significantly increased in compar-
ison with mild preeclampsia (maternal serum IL-8:
681.32 pg/ml (range: 140.40–1056.55 pg/ml) in se-
vere preeclampsia versus 140.40 pg/ml (range:
48.60–742.72 pg/ml) in mild preeclampsia (P5
0.05); maternal serum TNF-a: 15.95 pg/ml (range:
5.66–15.95 pg/ml) in severe preeclampsia versus
8.85 pg/ml (range: 4.06–14.79 pg/ml) in mild pre-
eclampsia (P50.01). There was no significant
difference in serum concentration of IL-6 between
patients with mild and those with severe preeclamp-
sia (P40.05).
Umbilical serum levels of IL-6 and IL-8 were
significantly increased in severe preeclampsia group
than in mild preeclampsia group. Umbilical serum
levels of IL-6 was found 118.31 pg/ml (range: 76.81–
546.35 pg/ml) in severe preeclampsia and 72.89 pg/
ml (range: 49.75–155.45) in mild preeclampsia.
Similarly umbilical serum levels of IL-8 in severe
and mild preeclampsia were 331.97 pg/ml (range:
147.96–670.70 pg/ml) and 130.85 pg/ml (range:
70.67–199.03 pg/ml), respectively. These differences
were statistically significant (P50.01). There was
no significant difference in the mean serum concen-
tration of TNF-abetween mild and severe pre-
eclampsia groups (P40.05).
Patients with preeclampsia were further divided
into two groups according to the presence of growth
retardation or not. Three were 12 pregnant patients
with preeclampsia complicated by IUGR. There
were statistically higher maternal serum levels of
IL-8 and TNF-ain patients with preeclampsia with
IUGR than in patients with preeclampsia with
normal fetal growth (700.90 pg/ml (range: 148.28–
1056.55 pg/ml) vs. 326.99 pg/ml (range: 48.60–
742.72 pg/ml) for IL-8, P50.05; 16.39 (range:
Table II. Analysis of maternal and umbilical serum levels of IL-6, IL-8, and TNF-ain patients with preeclampsia and in control subjects.
Mean +SD, median (range)
PPreeclampsia (n¼24) Normal pregnancy (n¼19)
Maternal serum
values(pg/ml)
IL-6 101.23 +121.02; 57.93 (30.19–669.79) 25.18 +24.46; 13.57 (5.45–476.45) 0.001**
IL-8 479.26 +318.96; 403.86 (140.40–1056.55) 89.46 +42.39; 88.70 (74.29–774.71) 0.001**
TNF-a15.03 +6.05; 14.93 (4.06–30.67) 6.98 +7.01; 4.5 (2.32–30.67) 0.001**
Umbilical cord
serum values(pg/ml)
IL-6 180.48 +178.65; 114.51 (43.57–712.89) 36.94 +28.56; 23.72 (7.48– 422.62) 0.001**
IL-8 3077.38 +1362.09; 254.58 (140.73–670.70) 154.35 +84.99; 135.02 (135.02–940.69) 0.013*
TNF-a19.45 +13.84; 15.95 (5.66–19.78) 10.57 +5.90; 9.18 (4.06–18.27) 0.006*
Mann–Whitney U-test was used.
*P50.05; **P50.01.
Table III. Maternal and umbilical serum levels of IL-6, IL-8, and TNF-ain mild preeclampsia and severe preeclampsia.
Mean +SD; median (range)
PMild preeclampsia (n¼9) Severe preeclampsia (n¼15)
Maternal serum
values (pg/ml)
IL-6 58.73 +26.45; 69.79 (30.19–333.87) 126.73 +147.65; 52.84 (112.89–669.79) 0.531
IL-8 284.52 +275.16; 140.40 (48.60–742.72) 596.10 +291.32; 691.32 (140.40–1056.55) 0.0 19*
TNF-a9.94 +3.77; 8.85 (4.06–14.79) 18.07 +5.05; 15.95 (13.92–30.67) 0.001**
Umbilical cord serum
values (pg/ml)
IL-6 80.59 +35.03; 72.89 (49.75–155.45) 240.42 +203.64; 118.31 (76.81–546.35) 0.002**
IL-8 126.84 +53.29; 130.85 (70.67–199.03) 4847.67+17214.61; 331.97 (147.96–67070) 0.001**
TNF-a24.96 +21.94; 15.81 (5.66–15.95) 16.15 +2.89; 16.39 (8.30–19.78) 0.676
Mann–Whitney U-test was used.
*P50.05; **P50.01.
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13.92–30.67) vs. 12.21 (range: 6.70–15.66 pg/ml)
for TNF-aP50.01, respectively). Umbilical serum
levels of IL-6 and IL-8 were found higher in patients
with preeclampsia complicated by IUGR than in
patients with preeclampsia with normal fetal growth.
These differences were statistically significant
(P50.05, P50.01, respectively) (Table IV).
In preeclamptic group, maternal serum concen-
tration of IL-8 was correlated with serum concentra-
tion in umbilical venous blood (r: 0.440; P: 0.031).
In control group, maternal serum concentration of
TNF-awas correlated with serum concentration in
umbilical venous blood (r: 0.759; P: 0.001). How-
ever, there were no statistical correlation with the
other cytokines between maternal serum and umbi-
lical venous blood (P40.05).
Discussion
This study demonstrated elevated concentrations of
inflammatory cytokines (IL-6, IL-8, and TNF-a)in
maternal and umbilical cord of preeclampsia when
compared with healthy pregnant women. The results
of this study also showed that increased maternal
serum levels of IL-8 and TNF-awere related with
the severity of preeclampsia. These findings point to
the importance of IL-6, IL-8, and TNF-ain the
pathophysiology of preeclampsia.
Endothelial damage and endothelial dysfunction
as a result of excessive maternal inflammatory
response to pregnancy by increasing proinflamma-
tory molecules, cytokines, and adhesion molecules
have been considered the key pathophysiologies of
preeclampsia [1,2,13]. IL-6 is produced by macro-
phages, monocytes, and endothelial cells and normal
human trophoblasts. It induces cell proliferation and
neutrophil mediated endothelial injury [14,15]. The
increased concentration of IL-6 in preeclampsia, as
observed in this study, is consistent with observations
by other authors [16–18]. Moreover, increased
production of IL-6 from the endothelial cells of
women with severe preeclampsia has been shown by
Takacs et al. [19]. Contrasting results were obtained
by Hayashi et al. [20], who reported that IL-6 in the
placenta and blood does not play significant role in
the induction of an immunologic imbalance in
preeclampsia. Al-Othman et al. [21] have also
reported that there was no significant difference in
the IL-6 levels in maternal serum between pre-
eclampsia and normotensive pregnant women. In
our study, we observed significantly higher concen-
tration of IL-6 in both maternal and umbilical serum
of patients with preeclampsia than in healthy
pregnant women.
In many studies, it was shown that IL-8 may play a
crucial role in the pathophsiology of preeclampsia
[18,22,23]. However, there are a few contrasting
results [16] that IL-8 serum levels did not differ
between preeclampsia and healthy pregnant women.
In this study, increased maternal and umbilical cord
serum IL-8 concentration was found in preeclampsia
in comparison with normal pregnant women. Similar
results were observed by Zhang et al. [22] who
demonstrated that maternal serum IL-8 concentra-
tion was higher in preeclampsia than in healthy
pregnant and nonpregnant women. In this study,
endothelial monolayer permeability was increased by
serum from women with preeclampsia but not from
healthy pregnant women or nonpregnant women.
Women with preeclampsia have higher leukocyte
counts and increased number of circulating neutro-
phils compared to normal pregnant group [24]. One
possible mechanism in preeclampsia is that abnormal
activation of neutrophils and monocytes cause
increased production of TNF-a, which in turn causes
endothelial dysfunction. In this study, maternal and
umbilical cord serum concentrations of TNF-awere
significantly higher in preeclampsia than in normal
pregnancy.
As it was reported that labor can affect the serum
levels of inflammatory markers [25,26] subjects that
in this study were not in labor and delivered by
cesarean section. Similarly, gestational age may
effects serum levels of interleukins, to avoid possible
Table IV. Serum concentrations of IL-6, IL-8, and TNF-abetween preeclamptic patients with intrauterine growth retardation or not.
Preeclampsia (mild and severe
preeclampsia) (n¼24)
Mean +SD; median (range)
PIUGR (þ)(n¼12) IUGR (7)(n¼12)
Maternal serum
values(pg/ml)
IL-6 103.46 +100.78; 52.5 (112.89–669.79) 99.0 +143.01; 72.5 (30.19–546.35) 0.862
IL-8 609.23 +308.56; 700.90 (148.28–1056.55) 349.28 +283.99; 326.99 (48.60–742.72) 0.028*
TNF-a18.84 +5.40; 16.39 (13.92–30.67) 11.21+3.96; 12.21 (6.70–15.66) 0.001**
Umbilical cord
serum values(pg/ml)
IL-6 268.09 +220.25; 133.8 (76.81–546.35) 92.87 +38.42; 81.47 (43.57–155.45) 0.015*
IL-8 5967.32 +19243.45; 353.49 (170.58–67070) 187.43 +170.39; 144.34 (30.85–693.31) 0.001**
TNF-a16.41 +3.04; 16.83 (8.30–19.78) 22.49+19.26; 15.15 (6.10–17.71) 0.436
IUGR, intrauterine growth retardation.
Mann–Whitney U-test was used.
*P50.05; **P50.01.
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confusion, both the study and control group were
chosen from the third trimester of pregnancy
(between 37 and 40 weeks). In many reported
studies, inflammatory cytokine levels in serum were
also studied according to trimesters [17,23,27,28].
However, even 1 week difference between the study
and control group may influence inflammatory
cytokine levels in serum. The type of anesthesia in
cesarean section may also affect the umbilical cord
serum levels cytokines, in this study both the
epidural and general anesthesia were used, which
could be considered as limitations of the study.
Ramsay et al. [29] reported that women with
preeclampsia have significantly impaired endothelial
function compared with healthy pregnant women. It
was shown that inflammatory cytokines impair
endothelium dependent relaxation [30]. They also
inhibit endothelial nitric oxide synthesis [31]. By
these mechanisms elevation of inflammatory cyto-
kines to some degree may responsible for endothelial
dysfunction seen in preeclampsia.
The results of the current investigation revealed a
significant elevation of umbilical serum IL-6 and IL-
8 but not TNF-ain preeclampsia compared with
normal pregnancy, implying alterations in circulating
cytokines of fetus in preeclampsia. To the best of our
knowledge, this is the first report describing umbi-
lical serum levels of IL-6, IL-8, and TNF-aduring
normal pregnancy and in preeclampsia.
In this study, significantly increased maternal
serum levels of IL-8 and TNF-awere found in
patients with preeclampsia with IUGR in comparison
with preeclamptic patients with normal fetal growth.
There were also higher levels of umbilical serum IL-6
and IL-8 in patients with preeclampsia complicated
by IUGR than in patients with preeclampsia with
normal fetal growth. Similar results were presented
by Laskowska et al. [23] who observed higher
concentrations of maternal and umbilical IL-8 in
preeclampsia with IUGR than in preeclampsia with
appropriate intrauterine growth. Although differ-
ences in maternal and umbilical IL-8 between
preeclamptic patients with IUGR and with normal
fetal growth were not statistically significant in this
study, they concluded that more advanced patholo-
gical changes in the placental and fetal circulatory
system in preeclamptic patients with IUGR result in
inadequate fetal oxygenation and nutrition leading to
fetal hypotrophia in these patients.
In conclusion, in this study it was observed that
altered endothelial function in preeclampsia is likely
related with increased concentrations of IL-6, IL-8,
and TNF-ain maternal serum. Increased concentra-
tions of IL-8, and TNF-ain maternal serum seemed
to be related with the severity of preeclampsia.
Greater inflammatory response by increased release
of IL-6, IL-8, and TNF-aas well as other proin-
flammatory cytokines might be associated with the
pathophysiology of preeclampsia. Alterations in
cytokine production may be one of the causes of
the pathological function in placenta and may result
in preeclampsia and IUGR.
Further studies with a larger patient cohort may
provide more meaningful data about the exact role of
cytokines in the development of preeclampsia.
Declaration of interest: The authors report no
conflicts of interest. The authors alone are respon-
sible for the content and writing of the paper.
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