The presence, severity, and onset of preeclampsia is associated with maternal interleukin-23 level: A case-control study
Background: Scientific evidence support that imbalance between inflammatory and anti-inflammatory cytokines play a critical role in preeclampsia (PE).
Objective: To investigate the relationship between the maternal serum level of interleukin (IL)-23, a pro-inflammatory cytokine, PE and its severity risk was investigated.
Materials and Methods: The case-control study included a total of 145 women counting 75 PE cases, 35 healthy pregnant and 35 healthy non-pregnant controls from Zahedan, southeast of Iran. The maternal levels of IL-23 in circulation were determined via enzyme-linked immunosorbent assay.
Results: The maternal serum levels of IL-23 were increased in PE and its 2 subgroups severe PE and mild PE, so that these increases were significant in PE and severe PE, but not in mild PE compared with the controls (p < 0.001 and p < 0.001, p = 0.08, respectively). Besides, the maternal IL-23 serum level was statically significant in the early onset PE, but not in the late onset-PE group compared to healthy pregnant controls (p < 0.001, p = 0.46 respectively).
Conclusion: The results of our study showed a positive association between IL-23 level and PE, especially in severe type and early onset PE, which suggests that IL-23 may be involved in the pathogenesis of this systemic syndrome.
Key words: Preeclampsia, Interleukin-23, Pregnancy, Inflammation.
 Magee LA, Nicolaides KH, Von Dadelszen P. Preeclampsia. New Engl J Med 2022; 386: 1817– 1832.
 Robillard PY, Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to lateonset preeclampsia. Am J Obstet Gynecol 2022; 226: S867–S875.
 Hurrell A, Duhig K, Vandermolen B, Shennan AH. Recent advances in the diagnosis and management of pre-eclampsia. Fac Rev 2020; 9: 10.
 Guan C, Zhao F, Yang Z, Tang Q, Wang L, Li X, et al. A review of key cytokines based on gene polymorphism in the pathogenesis of pre-eclampsia. Am J Reprod Immunol 2022; 87: e13503.
 Miller D, Motomura K, Galaz J, Gershater M, Lee ED, Romero R, et al. Cellular immune responses in the pathophysiology of preeclampsia. J Leukoc Biol 2022; 111: 237–260.
 Jahantigh D, Mousavi M, Forghani F, Javan MR, Movahedinia S, Rezaei M. Association between maternal circulating IL-27 levels and preeclampsia. Cytokine 2018; 102: 163–167.
 Abdo AIK, Tye GJ. Interleukin 23 and autoimmune diseases: Current and possible future therapies. Inflamm Res 2020; 69: 463–480.
 Li H, Tsokos GC. IL-23/IL-17 axis in inflammatory rheumatic diseases. Clin Rev Allergy Immunol 2021; 60: 31–45.
 El Shahaway AA, Abd Elhady RR, Abdelrhman AA, Yahia S. Role of maternal serum interleukin 17 in preeclampsia: Diagnosis and prognosis. J Inflamm Res 2019; 12: 175–180.
 Mohanakrishnan R, Beier S, Deodhar A. IL-23 inhibition for the treatment of psoriatic arthritis. Exp Opin Biol Ther 2022; 22: 59–65.
 Atzeni F, Siragusano C, Masala IF, Antonio C, Valentina P, D’Angelo S. IL-23 in axial spondyloarthritis and psoriatic arthritis: A good fit for biological treatment?. Expert Opin Biol Ther 2022; 22: 843–853.
 Cairns J, Monkley S, Tian S, Angermann B, Liu Z, Öberg L, et al. DOP06 deep characterization of IL23 pathway in different gut segments and associated plasma biomarkers in inflammatory bowel disease. J Crohn’s Colitis 2023; 17 (Suppl.): i64–i67.
 von Essen MR, Søndergaard HB, Petersen ERS, Sellebjerg F. IL-6, IL-12, and IL-23 STAT-pathway genetic risk and responsiveness of lymphocytes in patients with multiple sclerosis. Cells 2019; 8: 285.
 Rafat Sh, Mohamed YY, Ahmed ME, Abdelaleem EA. Interleukin-23 serum level in systemic lupus erythematosus patients: Relation to disease activity and different disease parameters. Egypt Rheumatol 2022; 44: 139–143.
 Lee KMC, Sherlock JP, Hamilton JA. The role of interleukin (IL)-23 in regulating pain in arthritis. Arthritis Res Ther 2022; 24: 89.
 Sewell GW, Kaser A. Interleukin-23 in the pathogenesis of inflammatory bowel disease and implications for therapeutic intervention. J Crohn’s Colitis 2022; 16 (Suppl.): ii3–ii19.
 Meng P, Zhao S, Niu X, Fu N, Su S, Wang R, et al. Correction: Ping Meng, et al. Involvement of the interleukin-23/interleukin-17 axis in chronic hepatitis C virus infection and its treatment responses. Int J Mol Sci 2016; 17: 1793.
 Abbasifard M, Arababadi MK, Bahrehmand F, Bazmandegan Gh, Shahrbabaki ZS, Kamiab Z. Gender affects IL23 serum levels in the hospitalized COVID-19 infected patients. Am J Clin Exp Immunol 2022; 11: 28–33.
 Eghbal-Fard S, Yousefi M, Heydarlou H, Ahmadi M, Taghavi S, Movasaghpour A, et al. The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia. J Cell Physiol 2019; 234: 5106–5116.
 Jahantigh D, Forghani F, Zidanloo SG. Interleukin-23 receptor (IL-23R) gene polymorphisms and haplotypes associated with the risk of preeclampsia: Evidence from cross-sectional and in silico studies. J Assist Reprod Genet 2019; 36: 1523–1536.
 Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol 2023; 23: 38–54.
 Hildenbrand K, Aschenbrenner I, Franke FC, Devergne O, Feige MJ. Biogenesis and engineering of interleukin 12 family cytokines. Trends Biochem Sci 2022; 47: 936–949.
 dos Santos Fagundes I, Brendler EP, Nunes Erthal I, Eder Ribeiro RJ, Caron-Lienert RS, Machado DC, et al. Total Th1/Th2 cytokines profile from peripheral blood lymphocytes in normal pregnancy and preeclampsia syndrome. Hypertens Pregnancy 2022; 41: 15–22.
 Braga A, Neves E, Guimarães J, Braga J, Vasconcelos C. Th17/regulatory T cells ratio evolution: A prospective study in a group of healthy pregnant women. J Reprod Immunol 2022; 149: 103468.
 Madadi S, Mohammadinejad S, Alizadegan A, HojjatFarsangi M, Dolati S, Samadi Kafil H, et al. Expression level of immune checkpoint inhibitory factors in preeclampsia. Hum Immunol 2022; 83: 628–636.