先兆子痫患者血清IL-18和IL-12的定量检测及其在发病机制中的作用研究

Quantitative Detection of the Serum IL-18 and IL-12 Contribute to the Pathogenesis of Preeclampsia

应用ELISA方法定量检测了20例正常未孕女性,20例健康妊娠孕妇,11例轻度、25例中度以及16例重度先兆子痫患者血清中IL-18与IL-12的含量。应用流式细胞术检测患者PBMC中Th1/Th2型细胞亚群的频率。健康妊娠孕妇血清中IL-18含量高于未孕女性(P<0.001),而IL-12的含量则要低于未孕女性(P=0.001)。先兆子痫患者血清中IL-18含量高于未孕女性(P<0.001),但与健康妊娠者无差别。轻、中度先兆子痫患者血清中IL-12含量低于未孕女性(P<0.05),中、重度先兆子痫患者血清中IL-12含量高于健康妊娠孕妇(P<0.05)。健康孕妇的IL-18/IL-12比值明显高于未孕女性,随先兆子痫病情严重程度,IL-18/IL-12比值逐渐降低且均低于正常妊娠孕妇。外周血中IL-2/IL-4的分泌比值及IFN-γ/IL-4的分泌比值,在健康未孕女性与健康妊娠孕妇组间无明显的统计学上的差异,但重度先兆子痫患者明显高于健康妊娠孕妇(P<0.01)。先兆子痫患者外周血Th1/Th2细胞亚群比值高于健康妊娠组,且与血清中IL-18/IL-12比值呈负相关(r=-0.535,P<0.001)。正常妊娠孕妇血清中IL-18的增加与IL-12的减少可能诱导Th2呈优势表达;而先兆子痫患者血清中IL-18与IL-12的同时增加可能促使Th1呈优势表达。

Background： Preeclampsia is a severe form of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive immune response. The cytokines are the core of the immune response process. Interleukin-18 （Interleukin-18, IL-18） could synergy with IL-12 to promote Th1 cell response, whereas IL-18 alone could able to induce the expression of Th2 cytokines. Methods： We used ELISA for quantitative detection the concentration of IL-18 and IL-12 in the serum from 20 cases of normal non-pregnant women, 20 cases of healthy pregnant women, 11 patients with mild, 25 moderate, and 16 cases of severe preeclampsia. The flow cytometry was used to detect the frequency of Th1/Th2 cell subsets in peripheral blood mononuclear cells. Results： The healthy pregnancy group had a higher concentration of serum IL-18 than nonpregnant women （P 〈0.001）, but had a lower concentration of serum IL-12 than non-pregnant women （P = 0.001）. The concentration of serum IL-18 in preeclampsia group was higher than that in nonpregnant women （P 〈0.001）, but with no difference from healthy pregnancy. Mild to moderate preeclampsia patients had a lower concentration of serum IL-12 than nonpregnant women （P 〈0.05）, and moderate to severe preeclampsia patients had a higher concentration of serum IL-12 than healthy pregnant women （P 〈0.05）. The IL-18/IL-12 ratio of the health pregnant women was significantly higher than non-pregnant women. And the IL-18/IL-12 ratio was gradually decreased with the severity of the preeclampsia, which was lower than normal pregnancy. There was no difference of the IL-2/IL-4 ratio or IFN-γ/IL-4 ratio in peripheral blood between nonpregnant women and healthy pregnancies pregnant women group, whereas it was higher in severe preeclampsia group than that in healthy pregnant women （P 〈0.01）. Moreover, the Th1/Th2 ratio was higher in preeclampsia patients than that in healthy pregnant group, which was negtive correlated with serum IL-18/IL-12 ratio （r = -0.535, P 〈0.001）. Conclusion： The increased serum IL-18 and the decreased IL-12 in normal pregnancy would induce Th2 response, whereas the increased concentration of both IL-18 and IL-12 in preeclampsia serum may promote Th1 as a predominantly immune response.