Determination of IL6,CRP, Liver Function Testsinwomen with Pregnancy Induce Hypertension in Tikrit City-Iraq
Dr.Alaa Saber Shihab,Department of Physiology, College of Medicine, Tikrit University, Salahaddine - Iraq.
Dr.MahaArshadHamdi,Department of Physiology, College of Medicine, Tikrit University, Salahaddine - Iraq.
Prof. Dr. MousaMahmoud Marbut,Department of Physiology, College of Medicine, Tikrit University, Salahaddine - Iraq.
Dr.saharKamelJwad, Department of Physiology, College of Medicine, Tikrit University, Salahaddine - Iraq.
Abstract:
Background: Abnormalities of cytokine IL6,CRP and other parameters in women with pregnancy induce hypertension (PIH) have been conformed in several studies.
Although their cause-effect relationships to PIH are not yet clear.Aim: To study the relationship of serum IL6,CRP and other parameters with pregnancy-induced hypertension. Patients andMethods: Fifty patients with gestational hypertension, 50 pregnant women as control, serum was collected to determine serum IL6,CRP, AST and ALT.
Results: Statistically significant differences were found in IL-6 level and CRP whereas a difference wasnot present in uric acid levels between PIH and control.In regard to liver function test,there is no significant differences of serum albumin were observed between PIH patients and controls,while there are significant differences regarding serum GGT,ALTandAST.
Key words: PIH, liver function, IL-6, CRP.
Introduction
Hypertension in pregnancy is a one of most prevalent disorder , representing about 10% of pregnant women, (1). ThePIH concederas major problem in hypertensive diseases complicating pregnancy in developing countries that affect both themortality and morbidity of mother and fetal health(2).
A- Oxidative stress, which can cause the formation of inflammatory factors lead to hypertension. B- Heredity andgenetic factors.C-Immunologic disorder can lead to PIH, and it is considered that the occurrence of hypertension in pregnancy is related to ischemic changes in placenta. It has been reported by many studies that the immunological hypothesis is improved in the PIH development (3-6).
Many studies have found that elevated IL-6 level in patients with PIH than that in patients with normal pregnancy,they found maternal and infant prognoses with high level of IL-6 are worse than those with normal IL-6 level, suggesting that IL-6 extend effects on the prognosis of patients withgestational hypertension, (7). Previous study, shown that elevations in inflammatory cytokines interleukin-6 play an exerts effect in the pathogenesis of hypertension,(8). It has been founded by scholars for several years that CRP is a non-specific inflammatory marker. However, recent years have recognized found a good relation between CRP and the pooroutcomes of pregnancy, such as PIHand stillbirth, (9,10).
Several hypotheses have been approaching for the pathogenesis of disease and includeimbalance of prostacyclin – thromboxane, immunogenic ,endothelial
dysfunction, and relative or absolute placental ischemia [11].
It is believed that "failings" in structure of normal hemochorial placental lead to PIH, (12).
The genetic factors of PIH is define, as women with positive family history of the PIH are three times more susceptible to suffer from it when they are pregnant,(13).
The aim of the study is to determine the IL6, CRP, AST and ALT in women with pregnancy induce hypertension in Tikrit city-Iraq.
Patients and Methods:
A case-control study,was don on fifty pregnant women attending with pregnant induce hypertension (PIH) treated in General Salah Alden Hospital onTikrit city from January to April 2018 0ther 50 normal healthy pregnant women at the same period were selected as the control group. The average age of these 100 pregnant women was 27.1±5.0 years.All of them assessed physically examination like blood presser
measurement. Patient with hypertension when systolic blood pressure was >140 mm Hg and diastolic blood pressure was >90 mm Hg .
The blood samples were taken after 12-14 hours of fasting for measuring serum lipid profile by standard clinical laboratory procedure.
IL-6 was assayed using Quantikine R and D systems,ELISA kit.CRPwas measured by using nephelometry method, uric acid, liver functions, (serum albumin,AST, ALT ,GGT)use spectrophotometric.
Statistical analysis was doneby chi square, student T test and one wayANOVA. All data values were expressed as mean ± standard deviation. P-values of less than 0.05or less were considered as statistically significant.
Results:
The present study included one hundred pregnant women; they were divided into fiftyhypertensive pregnant women, (PIH), and fifty pregnant women without hypertension as control group.
Table(1)show compares between serum of subjects associate inflammatory factors IL-6and CRP in pregnant induce hypertension(PIH), and control groups, there is significant difference was found Patients and controls, (8.17±2.4versus, 6.67±1.9, p<0.5), (18.2±8.3, versus , 7.5±2.5,p <0.05) respectively.
Table(2)In the present study, pregnant women with PIH had a significantly increase liver enzymes, (GGT, ALT and AST), ( 28.04±11.1versus ,20.1±6.2,p <0.05), (33.5±
8.5 versus, 26.6 ± 7.4 p <0.05), ( 29.9±7.1, versus, 23.2 ± 5.9,p <0.01) respectively as compared with normal pregnancy group.However, there was no significant difference concerning the serum albumin and uric acid between the patients and controls, (Table 2).
Table (1) show serum concentration of IL-6 and CRP in patients with PIH and normal pregnant control women.
Parameters PIH Patients Controls P value
IL6 (pg/ml) 8.17±2.4 6.67±1.9 <0.05
CRP (mg/ml) 18.2±8.3 7.5±2.5 <0.05
IL-6= interleukin-6; CRP=C-reactive protein, PIH= pregnancy induced hypertension.
Table (2)show characteristics of liver enzymes activities and serum
albuminconcentration in women with PIH and normal control pregnant women.
Parameters Patients Controls P value
GGT (mg/dl) 28.04±11.1 20.1±6.2 0.05
ALT (mg/dL) 33.5±8.5 26.6±7.4 0.05
AST(mg/dl) 29.9±7.1 23.2±5.9 0.01
Serum Albumin(mg/dl) 191.2±51.4 189.4±33 NS
uric acid 5.79±1.9 5.4±1.4 NS
AST=aspartate aminotransferase ,ALT=alanine aminotransferase, GGT= Gamma-GlutamylTransferase
Discussion
Many scholars believed that PIH is related with immune imbalance, and cytokines, especially inflammatory factors, had a significant roles in immune regulation.( 14). In the present study, the levels of IL-6 in patients with PIH were significantly higher than those in the normal pregnant women (p<0.05),this finding is agree with previous studies, (15,16). Also, Previous study found that Interleukin-6 (IL-6), stimulating angiotensin type 1 receptor lead to increaseangiotensin type 11which potent vasoconstriction (16, 17).
In the present study, there is significant elevation in serum CRP in patient with PIH as compare with normal pregnant women. C-reactive protein (CRP) which is a non- specific inflammatory-related protein produced by the liver and regulated by plasma interleukin-6, (18). Also, previous studies found that serum CRP was significantly elevated in patients with PIH, (19, 20,21).
It has been hypothesized that hypertension may be in part an inflammatory disorder.
Higher levels of CRP may increase blood pressure by reducing nitric oxide production in endothelial cells, causing vasoconstriction and increasing endothelin–1,(14, 22-24).
Another study done in china, the result of this study was not agree with the present study,(25).
Liver function test (LFT) abnormalities occur in 3% of the pregnancies, and usually
estrogen and progesterone produce during pregnancy, (26-28). In hypertensive pregnant women, liver enzymes activities, showed that AST, S.ALT and S.GGT were significantly higher in PIH patients as compare with controls.However, significant difference was not observed in albumin groups, (29-30).However, the present study disagrees about albuminan elevated level of ALT and AST in hypertensive pregnancy was also cited by some other studies, (31-32).
In present study serum GGT level was significantly increased in PIH patients when compared to controls. Similar results were documented by other studies, (33-34).
Conclusion
Results showed that the IL-6 protein level was positively correlated with pregnancy induce hypertension. . Recommendation
1-The results of these types of studies will be advantageous to further our knowledge of the pathophysiological ramifications associated with PIH and to further therapeutic development for this disease.
2- Further studies shouldbe perform for causative factor responsible for elevated IL6 production that subsequent PIH, and possible therapeutic intervention in the management of PIH.
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