Study On The Relationship Between IL-12 And VEGF In The Pathogenesis Of Pregnancy Induced Hypertension

Objective To detect the levels of serum interleukin 12(IL-12) and vascular endothelial growthfactor (VEGF),as well as investigate placental villi VEGF expression in patients with pregnancy induced hypertension (PIH) to explore the relationship between IL-12 and VEGF in pathogenesis of PIH.Methods Blood from 43 patients with PIH (PIH group) including 12 mild PIH, 13 moderate PIH and 18 severe PIH cases ;20 normal prirmigravid of third trimester (normal pregnancy group,NP group); 18 healthy nonpregnant women for maternal age (normal nonpregnant group, NNP group) was obtained prior to the onset of labor or medical intervention. Serum levels of IL-12 and VEGF were assessed using the quantitative sandwich enzyme immunoassay technique. The terminal villi were examined immuno-histochemically using monoclonal mouse anti-human VEGF immunoglobulin G.Results 1. The concentrations of serum IL-12 in PIH group(40.14 13.73 pg/ml) were significantly higher than those in normal pregnancy group (18.40 5.44pg/ml),P<0.01.Mild PIH group (23.17 5.71pg/ml) signifycantly higher than NP group, P < 0.05; moderate PIH group(37.95 5.61 pg/ml) significantly higher than mild group, P <0.01; severe PIH group (53.04 6.29pg/ml )significantly higher than moderate group, P < 0.01. NP group were significantly lower than those in NNP group (38.16 5.63 pg/ml), P <0.01.2. The concentrations of serum VEGF in PIH group (76.92+17.55 pg/ml) were significantly lower thnn those in NP group (103.23 + 14.84 pg/ml), P <0.01. No statistical significant difference between mild PIH group (94.72 13.43 pg /ml)and NP group,P>0.05;moderate PIH group(77.93 12.90pg/ml) significantly lower than mild group, P<0.01; severe PIH group (64.33 11.58 pg/ml)significantly lower than moderate group, P =0.05. NP group were significantly higher than those in NNP group (55.96 12.21pg/ml), P<0.01.3. Immunolocalization of VEGF in normal term villous placenta was observed in the syncytiotrophoblast, mesenchymal and vascular endothelialcells. In PIH group.the distribution of VEGF staining were similar to that of NP group, but with less intense. Computer image analysis (1) The expression of VEGF in placenta syncytiotrophoblast cells: There was no significant difference between mild PIH group and NP group, P > 0.05; also no difference was founded between moderate PIH group and mild PIH group, P > 0.05 moderate PIH group significantly higher than NP group, P <0.01;severe PIH group (preeclampsia and eclampsia) siasignificantly higher than moderate group, P <0.05.(2) The expression of VEGF in mesenchymal cells: severe PIH group significantly lower than NP group, P < 0.01.4. There was a significant negative borderline correlation between serum concentrations IL-12 and placenta VEGF in PIH group ( r = -0.73,P < 0.01) .Serum IL-12 concentrations were increased in three PIH subgroup, and negatively correlated with placenta VEGF expressions(mild r =-0.62, P <0.05 ; moderate r =-0.76, P <0.01 and severe r =-0.78, P <0.01 respectively). In NP group , a negative correlation was noted between the serum levels IL-12 and placenta VEGF expressions (r =-0.53, P <0.05).5. Logistic regression analysis showed an dependent association between serum IL-12 and VEGF levels in PIH group.Conclusions The relationship between serum levels of VEGF and IL-12 tended to be negatively correlated. There was a trend that serum IL-12 concentrations in PIH group increased with the severity of PIH and peaking in the severe PIH, those difference between PIH subgroups reach significance, while maternal serum VEGF levels were decreased in the patients with preeclampsia and correlated with the severity of PIH. These results suggest that high serum levels of IL-12 or low levels of VEGF may be observed in more advanced PIH patients. IL-12 may regulate VEGF in the patients diagnosed with PIH.