Modulation of Interleukin-35 In the Immune Response to H. Pylori Infection
Main Article Content
Abstract
Background: Infection with Helicobacter pylori is a common disease of the digestive system, normally associated with several degrees of gastritis as well as chronic inflammation. Interleukin-35 (IL-35) is an emerging anti-inflammatory cytokine that mediates regulatory immunity; however, little research has been directed toward its participation in the pathogenesis of H. pylori. Objectives: To assess serum IL-35 levels in patients infected with H. pylori and correlate them with the severity and duration of the disease. Methods: This cross-sectional study was done on 80 patients who were clinically suspected to be infected with H. pylori (44 males and 36 females; age range 15–63 years) attending Al-Najaf General Hospital, Iraq, from February 2024 to March 2025. Stool antigen tests confirmed the presence of H. pylori infection. Serum IL-35 concentrations were measured by a sandwich ELISA method. Classification of participants was done according to the status of infection (positive vs. negative), severity of gastritis (mild, moderate, severe), and chronicity of the infection (acute vs. chronic). Results: Out of 80 participants, 58 (72.5%) were positive for H. pylori. The levels of IL-35 were significantly decreased in H. pylori-positive individuals (48.37 ± 22.33 pg/ml) as compared to negatives (58.54 ± 11.45 pg/ml, p =0 .0456). Among the infected patients, the levels of IL-35 varied significantly with the severity of gastritis; mild (35.7 ± 8.09), moderate (51.3 ± 11.11), severe (60 .2 ±17 .22) (F=21 .5, p<0 .0001). The concentrations of IL-35 were also significantly higher in chronic cases (62 .54±12 .32 pg/ml) than acute cases (34 .22±8 .54 pg/ml, p=0.000). Conclusions: IL-35 is low in early H. pylori infection and seems to go up with more gastritis severity and duration, hinting a modulatory role in the host immune response. These findings support potential involvement of IL-35 in immunopathogenesis and progression of H. pylori related gastric inflammation.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Al-Fahham, A.A. (2018) Development of New LSD Formula when Unequal Observations Numbers of Observations Are. Open Journal of Statistics, , 8, 258-263.https://doi.org/10.4236/ojs.2018.82016.
Bassagh, A., Hayatbakhsh Abasi, M., Larussa, T., Ghazizadeh, M., Nemati, M., Mirkamandar, E., & Jafarzadeh, A. (2018). Diminished circulating concentration of interleukin-35 in Helicobacter pylori-infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients. Helicobacter, 23(4), e12501. https://doi.org/10.1111/hel.12501
Collison, L.., Chaturvedi, Vandana., Henderson, Abigail L.., Giacomin, P.., Guy, C.., Bankoti, Jaishree., Finkelstein, D.., Forbes, K.., Workman, C.., Brown, Scott A.., Rehg, J.., Jones, Michael L.., Ni, H.., Artis, D.., Turk, M.., & Vignali, D.. (2010). IL-35-mediated induction of a potent regulatory T cell population. Nature Immunology , 11 , 1093-1101 . http://doi.org/10.1038/ni.1952
Conteduca, V.., Sansonno, D.., Lauletta, G.., Russi, S.., Ingravallo, G.., & Dammacco, F.. (2013). H. pylori infection and gastric cancer: state of the art (review).. International journal of oncology , 42 1 , 5-18 . http://doi.org/10.3892/ijo.2012.1701
Ding, Y., Chen, D., Tarbell, K. V., & Cheng, G. (2012). IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. PLoS ONE, 7(3), e33628. https://doi.org/10.1371/journal.pone.0033628
Hadi, W. S., Salman, R. S., Al-Fahham, A. A., Khan, M. U. F., Kadir, S., Laft, M. H., Saeed, B. Q., Kadhum, W. R., Jalil, A. T., & Kadhim, M. M. (2022). Evaluation of IL-17 and IL-35 in patients with giardiasis in Thi-Qar province, Iraq. Journal of Medicine and Life, 15(9), 1096–1099. https://doi.org/10.25122/jml-2021-0328
Hooi, J.., Lai, Wan Ying., Ng, Wee Khoon., Suen, M.., Underwood, F.., Tanyingoh, D.., Malfertheiner, P.., Graham, D.., Wong, V.., Wu, Justin C.Y.., Chan, F.., Sung, J.., Kaplan, G.., & Ng, S.. (2017). Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis.. Gastroenterology , 153 2 , 420-429 . http://doi.org/10.1053/j.gastro.2017.04.022
Kao, J.., Zhang, Min., Miller, Mark J.., Mills, J.., Wang, Baomei., Liu, Maochang., Eaton, K. A.., Zou, W.., Berndt, B.., Cole, T.., Takeuchi, T.., Owyang, S.., & Luther, Jay. (2010). Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice.. Gastroenterology , 138 3 , 1046-54 . http://doi.org/10.1053/j.gastro.2009.11.043
Li, Xinyuan., Mai, J.., Virtue, A.., Yin, Ying-Xuan., Gong, Ren., Sha, Xiaojin., Gutchigian, Stefanie., Frisch, A.., Hodge, I.., Jiang, Xiaohua., Wang, Hong., & Yang, Xiaofeng. (2012). IL-35 Is a Novel Responsive Anti-inflammatory Cytokine — A New System of Categorizing Anti-inflammatory Cytokines. PLoS ONE , 7 . http://doi.org/10.1371/journal.pone.0033628
Liebregts, T.., Adam, B.., Bredack, Christoph., Gururatsakul, M.., Pilkington, K. R.., Brierley, S.., Blackshaw, A.., Gerken, G.., Talley, N.., & Holtmann, G.. (2011). Small Bowel Homing T Cells Are Associated With Symptoms and Delayed Gastric Emptying in Functional Dyspepsia. The American Journal of Gastroenterology , 106 , 1089-1098 . http://doi.org/10.1038/ajg.2010.512
Malfertheiner, P.., Camargo, M. C.., El-Omar, E.., Liou, Jyh-Ming., Peek, R.., Schulz, C.., Smith, Stella I., & Suerbaum, S.. (2023). Helicobacter pylori infection. Nature Reviews Disease Primers , 9 , 1-24 . http://doi.org/10.1038/s41572-023-00431-8
Menam Mtsher, A., Raheem, N. A., & Al fahham, A. A. (2024). Biochemical characteristics and clinical significance of IL 35: A review article. International Journal of Health & Medical Research, 3(12), 868-872. https://doi.org/10.58806/ijhmr.2024.v3i12n06
Mills, K.. (2022). IL-17 and IL-17-producing cells in protection versus pathology. Nature Reviews. Immunology , 23 , 38 - 54 . http://doi.org/10.1038/s41577-022-00746-9
Saraiva, M.., Vieira, P.., & O’Garra, A.. (2019). Biology and therapeutic potential of interleukin-10. The Journal of Experimental Medicine , 217 . http://doi.org/10.1084/jem.20190418
Zamani, M.., Ebrahimtabar, F.., Zamani, V.., Miller, W. H.., Alizadeh-Navaei, Reza., Shokri-shirvani, J.., & Derakhshan, M.. (2018). Systematic review with meta‐analysis: the worldwide prevalence of Helicobacter pylori infection. Alimentary Pharmacology & Therapeutics , 47 , 868 - 876 . http://doi.org/10.1111/apt.14561