pre - eclampsia ( pe ) is a pregnancy associated disorder known by hypertension and proteinuria .
the etiology of pe is not fully understood and a great number of mechanisms are proposed as the disease pathophysiology ; however , the only definite cure of this syndrome is delivery .
it is a general consensus on the role of disruption between vascular generation and anti - angiogenic responses in creating pe .
in addition , immune mal - adaptation hypothesis suggests that pe is the result of an inappropriate regulation of the normally t helper 2 deviated response during the pregnancy . in this way
recent reports suggest that pe is associated with a th1 predominant profile while activation of the immune system leads to alteration in cytokine profile and defect in the acquisition of invasive phenotype by trophoblasts in pe patients .
the first 2 stages of disease cause dysfunction in uteroplacental perfusion and oxidative stress while the 3 stage of pe is due to the release of inflammatory and angiogenic factors , which could lead to maternal endothelial damage and systemic inflammatory response .
cytokines , growth factors , and adhesion molecules have been proposed as important mediators for successful placentation as well as endothelial function . over past decades , multiple analyses of cytokines provided substantial insight into the key players of the maternal immune system involved in pe .
tumor necrosis factor- ( tnf- ) is an inflammatory cytokine produced by human uterine and placental cells at the early and late stages of gestation and promotes the regulation of trophoblast growth and invasion .
furthermore , tnf- could inhibit deeply integration and invasion of trophoblasts in maternal endometrium , which leads to pe .
interleukin-15 ( il-15 ) , which is also a proinflammatory cytokine , has profound effects on natural killer ( nk ) cells and their cytotoxicity activation .
regarding to the role of nk cells in the pathogenesis of pe , il-15 could be a key player in development of disease .
interleukin-10 ( il-10 ) as an anti - inflammatory cytokine is produced by some subpopulations of t lymphocytes , monocytes , macrophages , and cytotrophoblasts .
production of this cytokine is considered to play an important role in maternal immune tolerance of the fetus in normal pregnancy . in this study
, we compared the serum levels of tnf- , il-15 , and il-10 in iranian pe women with normotensive ones .
the study was a case - control study , in which serum samples of 84 pregnant women were studied .
44 pe ( cases ) and 40 normotensive ( controls ) pregnant women were enrolled in this study .
these 2 groups were selected among the women admitted to a university associated hospital of tehran university of medical sciences .
pe patients were diagnosed by hypertension ( blood pressure  140/90 mm hg ) and proteinuria ( at least 2 + on dips teak examination or  300 mg/24 h on at least 2 occasions 6 h apart ) after the 20 week of gestation .
the pe women were under the supervision and treatment of obstetrics and gynecology specialist during pregnancy .
the normotensive control group consisted of healthy women with uncomplicated pregnancy who referred for normal routine check - up examinations to a university associated hospital .
pregnant women with pre - gestational diabetes mellitus and chronic hypertension were excluded from the study .
5 ml of venous blood sample were taken from both groups before beginning of the active phase of labor .
serum levels of tnf- and il-10 were measured using a sandwich elisa test due to manufacturer 's instruction ( bender medsystems , austria ) .
the levels of il-15 were assayed by using il-15 sandwich elisa kit ( r&d systems , minneapolis , mn ) . in
above mentioned elisa kits routine procedures were done in this order ; coating the plate with capture antibody , blocking the plate , adding standards , and unknown samples , washing , adding the biotin conjugated specific antibody , washing , applying enzyme - linked streptavidin , and finally adding chemical substrate .
optical density of color chemicals that produced in the wells of the plate were read and the concentrations of cytokines were measured according to plots .
the serums that their cytokine levels were beyond the upper limit of the kit were diluted for assessment .
for all mentioned cytokines , standard curves were plotted and the concentrations were calculated according the manufacturer 's instruction .
student 's t - test was used for comparison between serum levels of two groups . p value
there was no statistically significant difference related to age and gestational age at the time of sampling between two groups ; however , there were higher systolic and diastolic pressures in pe group compared to normotensive one ( p values : 0.01 and 0.03 respectively for systolic and diastolic blood pressures ) .
the women with pe showed significantly higher serum concentrations of tnf- and il-15 ( p values : 0.001 and 0.01 respectively ) relative to the control group . in comparison ,
levels of il-10 in the serum of normotensive pregnant women were significantly higher than pe patients ( p value = 0.01 ) .
clinical characteristics of the preeclamptic and normotensive women serum levels of tumor necrosis factor- in preeclamptic ( pe ) and normal subjects .
each bar represented 44 pe and 40 normotensive pregnant women serum levels of interleukin-15 in preeclamptic ( pe ) and normal subjects .
each bar represented 44 pe and 40 normotensive pregnant women serum levels of interleukin-10 in preeclamptic ( pe ) and normal subjects .
results of this study demonstrated that in women having pe , compared to women with a normal pregnancy , inflammatory th1-type responses are increased ; while anti - inflammatory responses are decreased .
the higher levels of pro - inflammatory cytokines ( tnf- and il-15 ) and lower levels of il-10 in the pe group suggest an increased inflammatory status in pe during last months .
sharma et al . and xie et al . , in agree with our results , found that the level of inflammatory cytokines such as tnf- increased significantly in preeclamptic patients compared with health controls .
furthermore , laskowska et al . in consistent with us , indicated that tnf- increased in pe patients and suggested this cytokine may be play a role in pathogenesis and consequences of pe .
in general , these studies demonstrated that tnf- is a potent pro - inflammatory cytokine , its primary biological activity includes inflammation and it may contribute to the abnormal placental invasion . however , afshari et al . and jonsson et al . observed no significant changes of tnf- in pe women compared to normal pregnant women .
. showed upraised serum levels of il-15 in pe cases compared to normotensive ones . in line with this finding , el - baradie et al . in their study indicated that serum levels of il-15 and il-16 were elevated in pe relative to normotensive pregnant women .
in contrast lu et al . represented not elevated levels of il-15 in pe subjects compared to normal women . in normal pregnancy ,
it seems that in pe th1-type cytokines such as tnf- and ifn- induce trophoblastic apoptosis , inhibit differentiation and invasion of trophoblast , and finally , may be involved in the incomplete invasion of trophoblast to spiral arteries ; pathologic processes that are integral parts of pe .
our findings showed higher levels of il-10 , which is an anti - inflammatory cytokine in sera of normal pregnant women .
in concordance with our results , sharma et al . showed that il-10 was decreased significantly in pe patients compared to normal pregnant women .
inversely , bakheit et al . and xie et al . found higher serum levels of il-10 in pe women and jonsson et al . observed no significant difference in il-10 levels between normotensive and pe women .
these contradictory results of various studies could be related to sampling in different stages of pregnancy . pe as an inflammatory process starts from the first steps of placentation ; however , this inflammatory grade lasts until parturition .
consequently , upraised levels of pro - inflammatory cytokines in our study may be the perquisite of pe .
recognition of early detectable inflammatory markers could be a great help to predict and observe pe patients more accurately .
 background : pre - eclampsia ( pe ) is a pregnancy associated disorder characterized by hyper - tension and proteinuria . the first 2 stages of pe cause dysfunction in uteroplacental perfusion and oxidative stress while the third stage of pe is due to the release of inflammatory and angiogenic factors , which could lead to maternal endothelial damage and systemic inflammatory response . in this study , we compared the serum levels of tumor necrosis factor- ( tnf- ) , interleukin-15 ( il-15 ) , and interleukin-10 ( il-10 ) in pe and normotensive women.materials and methods : serum samples of 84 pregnant women ( 44 pe and 40 normotensive ) were evaluated for tnf- , il-15 and il-10 by sandwich elisa assay.results:the women with pe showed significantly higher serum levels of tnf- and il-15 ( p = 0.001 and 0.01 respectively ) in comparison with normotensive pregnant women . 
 conversely , the serum levels of il-10 in normotensive women were significantly higher compared to pe patients ( p = 0.01).conclusion : the results of this study demonstrated that inflammatory t helper 1-type responses are increased in pe women compared to normotensive pregnant women . 