A STUDY OF THE ROLE OF CYTOKINES IMBALANCE AND OXIDATIVE STRESS IN THE PATHOGENESIS OF PREECLAMPSIA IN KHARTOUM TEACHING HOSPITAL

Abstract

Preeclampsia remains a major cause of maternal and perinatal morbidity and mortality. Its exact aetiology is still obscure. Objectives: The objective of this case control prospective study which was conducted in Khartoum Teaching Hospital during the period (2007-2008) was to study the role of cytokines imbalance and oxidative stress in the pathogenesis of preeclampsia. Methodology: The levels of interferon gamma (IFN-γ), as Th1 cytokine and interleukin- 4 (IL-4), interleukin-10 (IL-10) as Th2 cytokines were determined using Enzyme-linked immunosorbent assay (ELISA) in sera from 33 women with preeclampsia (at presentation and 7 days later) and 32 women with normal pregnancy as a control group. In order to study the effect of the oxidative stress on pathogenesis of preeclampsia, the activity levels of the erythrocyte antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were determined in 37 women with preeclampsia compared to 38 women with normal pregnancy in the third trimester using ELISA, and omega-3 (Eicosapentaenoic acid ; EPA & Docosahexaenoic acid; DHA) and omega-6 (arachidonic acid) profiles in three erythrocyte membrane phospholipids fractions; phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphyngomyelin, using gas chromatography. Further more, the plasma antioxidant vitamins; retinol and α-tocoferol, were also determined using HPLC. Results: at presentation, the levels of IFN-γ and IL-4 were slightly—not statistically significant— higher in the women with preeclampsia whereas IL-10 was significantly higher in the women with preeclampsia (P=0.002). Seven days later the women with preeclampsia had significantly lower levels of IFN-γ (P=0.035) and IL-4 (P=0.000) and 7 significantly higher levels of IL-10 (P=0.000). There were no significant differences in the levels of the three antioxidant enzymes in preeclamptic women compared to women with normal pregnancy. Women with mild preeclampsia (Diastolic blood pressure (DBP) < 110) have slightly higher (not statistically significant) level of activity of erythrocyte glutathione peroxidase, and lower activity levels of catalase and superoxide dismutase compared to women with severe preeclampsia (DBP≥ 110). A significantly negative correlation was observed between the activity of glutathione peroxidase and diastolic blood pressure, r= -0.371, P = 0.02. In the three phospholipids fraction (PE, PC & sphyngomyelin), the mean level of EPA was significantly higher in women with preeclampsia than the control group P = 0.012, 0.000, 0.000 respectively. The mean level of DHA was significantly higher in women with preeclampsia than the control group, P= 0.04, 0.046, 0.000 respectively. The mean level of arachidonic acid was only significantly higher in women with preeclampsia in the sphyngomyelin fraction P=0.000. When comparing women with mild and severe preeclampsia there was no statistically significant difference in fatty acids profiles. The median level of α-tocopherol was significantly higher in women with preeclampsia than the control group, P = 0.026. No significant difference was noted between the two groups regarding retinol level. Conclusion: The study findings do not support oxidative stress, but are in favor of involvement of cytokines imbalance in the pathogenesis of preeclampsia.