Systemic inflammatory response in exacerbation of cytomegalovirus infection in women in the second trimester of pregnancy

Aim. To study the systemic inflammatory response during exacerbation of cytomegalovirus infection (CMVI) in women in the second trimester of pregnancy.

Materials and methods. 120 women were examined at 21-24 weeks of pregnancy, uncomplicated and complicated CMVI. The 1st group included 30 seronegative healthy pregnant women, the 2nd group - 30 patients with similar gestational periods, complicated by latent CMVI and placental insufficiency, the 3rd group - 30 pregnant women with exacerbation of CMVI and placental insufficiency, and the 4th group - 30 pregnant women with exacerbation of CMVI, leading to placental insufficiency and the threat of miscarriage.

Results. In women of the first group, the concentration of TNF-a in the blood serum was 13.5 (11.5-30.3) pg/mL, IFN-y - 134.4 (114.2-151.3) pg/mL, IL-1P - 18.0 (13.4-36.3) pg/mL, IL-6 - 1.90 (1.40-3.30) pg/mL, IL-4 - 26.2 (20.3-55.4) pg/mL and IL-2 - 27.9 (18.2-38.0) pg/mL. In group 2, compared with group 1, an increase in the median of TNF-a was 1.37 times (p=0.043) and IL-2 was 1.25 times (p=0.025), which was explained by moderate activation of systemic inflammation in latent CMVI. In group 3, in contrast to group 2, the level of TNF-a increased by 3.45 times (p=0.000001), IFN-y - by 1.69 times (p=0.000001), IL-1P - by 4.37 times (p=0.000001), IL-6 - 1.78 times (p=0.000001), IL-2 - 2.21 times (p = 0.000001) and the concentration of IL-4 decreased 2.11 times (p=0.000063). This indicated an imbalance of pro- and antiinflammatory cytokines, increasing the risk of miscarriage. In group 4, in comparison with group 3, a 1.5-fold increase in TNF-a was recorded (p=0.0052), IFN-y was 1.38 times (p=0.00015), IL-1P was 1.67 times (p=0.0000001), IL-6 - 1.67 times (p=0.0035), IL-2 - 1.37 times (p=0.008) with a decrease in the level of IL-4 in 1.29 times (p=0.0030) in the setting of clinical and sonographic signs of placental insufficiency and the threat of termination of pregnancy.

Conclusion. The increase in the concentration of pro-inflammatory cytokines (TNF-a, IFN-y, IL-1P, IL-2, IL-6) and the decrease in the level of anti-inflammatory cytokine (IL-4) in patients with exacerbation of CMVI in the second trimester of pregnancy, complicated by placental insufficiency, associated with the threat of miscarriage, confirm the role of activation of the systemic inflammatory response in the pathogenesis of initiation of premature labor.

1. Lomova N.A., Ordzhonikidze N.V, Vanko L.V. Systemic inflammatory response syndrome and pregnancy (a review of literature). Akusherstvo i Ginekologiya 2012; (1):23-27 (in Russian).

2. Serov V.N. Features of infection in obstetrics, gynecology and perinatology. Russkiy meditsinskiy zhurnal 2006; 14(1): 2-5 (in Russian).

3. Sukhikh G.T., Vanko L.V. Immune factors in the etiology and pathogenesis of pregnancy complication. Akusherstvo i Ginekologiya 2012; (1): 128-136 (in Russian).

4. Ishutina N.A., Andrievskaya I.A., Dorofienko N.N. Malon dialdehyde and tumor necrosis factor alpha at cytomegalovirus infection during pregnancy. Bulleten' fiziologii i patologii dyhania = Bulletin Physiology and Pathology of Respiration 2015; (55):78-81 (in Russian).

5. Serov V.N., Manukhin I.B., Kuz’min VI. Cytomegalovirus infection in the pathology of pregnancy and the fetus. Akusherstvo i Ginekologiya 1997; (6): 16-19 (in Russian).

6. Strizhakov A.N., Voloshchuk I.N., Timokhina E.V., Kozlova U.A. Morphofunctional changes in the placenta with placental insufficiency of varying severity. Voprosy ginekologii, akusherstva iperinatologii 2010; 9(2): 5-11 (in Russian).

7. Milovanov A.P. Pathology of the mother-placenta-fetus system. Moscow: Meditsina; 1999 (in Russian).

8. Tetruashvili N.K., Sidel’nikova V.M., Veryasov V.N., Sukhikh G.T. The role of the cytokine system in the pathogenesis of habitual miscarriage and premature birth. VestnikRossiyskoy assotsiatsii akusherov iginekologov 1999; (3):34-44 (in Russian).

9. Sukhikh G.T., Van’ko L.V Immunology of pregnancy. Moscow: RAMS; 2003 (in Russian).

10. Kuleshov V.M., Shvayuk A.P., Gorbenko O.M., Obukhova O.O., Ilizarova N.A., Trunova L.A., Trunov A.N., Sol-odyankina A.N. Features of the balance of cytokines in serum during pregravid preparation of women with habitual miscarriage. Akusherstvo i Ginekologiya 2007; (6):39-43 (in Russian).

11. Freidlin I.S. Immunophysiology of endothelial cells. Human Phusiology 2006; 32(3):357-367.

12. Potapnev M.P. Neutrophil cytokine network in inflammation. Immunologiya 1995; (4):34-40 (in Russian).

13. Freydlin I.S. The key position of macrophages in the cytokine regulatory network. Immunologiya 1995; (3):44-48 (in Russian).

14. Gazieva I.A., Chistiakova G.N. Features of the cytokine regulation of endothelial hemostasiological interactions in threatening pregnancy interruption in the first trimester. Rossiyskiy vestnik akushera-ginekologa 2008; 8(2):16-20 (in Russian).

15. Bashmakova N.V., Motornyuk Yu.I. Features of the immune response depending on the nature of the course of urogenital chlamydial infection in pregnant women. Rossiyskiy vestnik akushera-ginekologa 2001; (2):8—11 (in Russian).

16. Gomez-Lopez N., Romero R., Plazyo O., Panaitescu B., Furcron A.E., Miller D., Roumayah T., Flom E., Hassan S.S. Intra-amniotic administration of HMGB-1 induced spontaneous preterm labor and birth. Am. J. Reprod. Immunol. 2016; 75(1):3-7. doi: 10.1111/aji.12443