The role of chronic systemic inflammation syndrome in pregnant cows in the development of antenatal liver pathology in newborn calves

Studies have been conducted to study the effect of the cytokine profile of cows with chronic systemic inflammation syndrome in the third trimester of pregnancy on the hematobiochemical  status  of  newborn  calves. The  experiment  was  conducted  on  redmottled  cows,  which  were  divided  into  2 groups: group 1 (n = 15) – clinically healthy cows  with  uncomplicated  pregnancy,  average fatness 3.6 ± 0.16 points, group 2 (n = 7) – cows with lowintensity chronic systemic inflammation  syndrome,  average  fatness 4.4±  0.20  points.  At  the  beginning  of  the third  trimester  of  pregnancy,  blood  serum samples were taken from cows to determine the  level  of  interleukin-1β  (IL-1β),  tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2),  interleukin-4  (IL-4),  interleukin-10  (IL-10) and interferon-γ (INF-γ). On the 3rd day after birth, blood samples were taken from the received calves for analysis. The above cytokines  and  hematobiochemical  parameters  were  determined.  It  was  found  that  in calves from group 2, the level of IL-2, IL-4, IL-10 and INF-γ was lower than the comparison group by 10.0; 29.3; 24.5 and 17.4%, respectively,  and  IL-1ß  and  TNF-α  were 45.8  and  8.7%  higher.  Spearman's  correlation analysis showed that there is a significant direct correlation of noticeable and high strength  between  the  level  of  cytokines  of maternal cows and similar indicators in newborns, which indicates the influence of signaling proteins of the mother's body on fetal development.  As  a  result,  neonatal  hepatodystrophy  was  diagnosed  in  calves  born from cows with chronic systemic inflammation  syndrome,  accompanied  by  cytolysis and  cholestasis  syndrome,  accumulation  of endotoxins  and  a  decrease  in  energy  substrates. The data obtained show that a change in  the  cytokine  profile  during  pregnancy towards  the  predominance  of  proinflammatory  cytokines  creates  a  risk  of developing  antenatal  liver  pathology  in  future offspring, thereby forming prerequisites for the development of comorbid pathology in newborns.

1. Vostroilova G.A., Parshin P.A., Zhukov M.S., Khokhlova N.A., Shabanov D.I., Korchagina A.A. The state of the prooxidant-antioxidant system in cows with different clinical conditions during pregnancy. International Bulletin of Veterinary Medicine. 2023; 2: 301- 311. DOI: 10.52419/issn2072-2419.2023.2.301

2. Zhukov M.S., Alyokhin Yu.N. Indicators of morbidity and survival of newborn calves with different body weight. Veterinary medicine. 2020; 11: 44-48. DO IT: 10.30896/0042-4846.2020.23.11.44-48

3. Lebedeva E.S., A Bagaev.V., Chulkina M.M., Pichugin A.V., Ataullakhanov R.I. NF-KB, but not the Mark-signaling pathway determines the synergistic response of macrophages to simultaneous activation of two types of TLR4 + NOD2 or TLR9 + NOD2 receptors. Immunology. 2017; 38 (2): 76-82. DOI: 0.18821/0206-4952-2017-38-2-76-82

4. Parshin P.A., Vostroilova G.A., Brigadirov Yu.N., Shaposhnikov I.T., Zhukov M.S., Sashnina L.Yu., Akulova K.O., Yakimchuk O.V. Immune status of cows with different gestation periods and in the early postpartum period. Veterinary Pharmacological Bulletin. – No. 3 (24). – pp. 65-80. DOI: 10.17238/issn2541-8203.2023.3.65

5. Chesnokova N.P., Yakhamova N.N., Arkhangelsky S.M. On the role of violations of the immune status of the mother and fetus in the pathogenesis of gestosis. Saratov Journal of Medical Science 2008; 22 (4): 26-29.

6. Shakhov A.G., Alyokhin Yu.N., Shabunin S.V., Sashnina L.Yu., Fedosov D.V., Erin T.A., Prigorodova O.V., Sidelnikova I.R. Methodological guide for the diagnosis and prevention of disorders of antenatal and intranatal origin in calves. GNU VNIVIPFiT, Voronezh: Istoki Publishing House, 2013; 92 p.

7. Shcherbakov V.I., Ryabichenko T.I., Skosyreva G.A., Obukhova O.O., Trunov A.N. Possible influence of ectopic and placental inflammation on activation of the immune system of a pregnant woman and programmed fetal development. Russian Bulletin of the obstetriciangynecologist. 2021; 21 (2): 14–20. DOI: 10.17116/rosakush20212102114

8. Shcherbakov V.I., Skosyreva G.A., Ryabichenko T.I., Obukhova O.O. Cytokines and regulation of glucose and lipids in obesity. Obesity and metabolism. 2022; 19 (3): 317-323. DOI: 10.14341/omet12863

9. Yakornova G.V., Remizova I.I., Chistyakova G.N., Ustyantseva L.S. Dynamics of proinflammatory cytokines in children born to women with complicated pregnancy, depending on the course of the early period of adaptation. Russian Bulletin of Perinatology and Pediatrics. 2015; 4: 50-56.

10. Alam S.M.K., Konno T., Dai S., Lu L., Wang D., Dunmore J.H., Godwin A.R., Soares M.J. The cytokine of decidual uterine cells provides pregnancy-dependent adaptation to a physiological stressor. Development. 2007; 134 (1): 407-415. DOI:10.1242/dev.02743

11. Burton G.J., Fauden A.L., Thornburg K.L. Placental origins of chronic diseases. Physiol Rev. 2016; 96 (4): 1509-1515. DOI 10.1152/physrev.00029.2015.

12. Kolotta F., Re F., Muzio M., Bertini R., Polentarutti N., Sironi M., Giri J.G., Dower S.K., Sims J.E., Mantovani A. Interleukin-1 receptor type II: a bait target for IL-1, which is regulated by IL-4. Science 1993; 261:472-475. DOI: 10.1126/science.8332913

13. Kumagai T., Matsukawa N., Kaneko Yu., Kusumi Yu., Mitsumata M., Uchida K. Inflammatory mediator resulting from lipid peroxidation: identification of 4-hydroxy-2-nonenal as a potential inducer of cyclooxy-genase-2 in macrophages. J Biol Chem 2004; 279: 48389-48396. DOI:10.1074/jbc.M409935200

14. Li L., Yang G., Shi S., Yang M., Liu H., Boden G.Fat triglyceride lipase, adiponectin and visfatin are suppressed by tumor necrosis factor-alpha (TNF-alpha) in vivo. Cytokine. 2009; 45(1): 12-19. DOI: 10/1016/j.cyto.2008.10.006

15. Parameshwaran N., Patial S. Tumor necrosis factor - signaling in macrophages. A critical review of eukaryotic gene expression. 2010; 20: 87-103. DOI: 10.1615/critreveukargeneexpr.v20.i2.10

16. Shi J., Fan J., Su K., Yang Z. Cytokines and disorders of glucose and lipid metabolism. Anterior endocrinol (Lausanne). 2019; 10: 703. DOI: 10.3389/fendo.2019.00703

17. Somm E., Henrisho E., Pernin A., Judge-Aubrey S.E., Mazzin P., Dyer J.M., Niklin M.J., Meyer S.A. Reduction of fat mass in mice with deficiency of interleukin-1 receptor antagonists. Diabetes. 2005; 54(12): 3503 -3509. DOI: 10.2337/diabetes.54.12.3503.

18. Zarate M.A., Wesolowski S.R., Nguyen L.M., De Dios R.K., Wilkening R.B., Rozans P.J., Wright K.J. Intrauterine inflammatory process induces early activation of the innate immune response of the liver in a sheep fetus in late pregnancy. Innate immunity. 2020; 26(7): 549-564.