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Ahmadi, A.* ; Yousefimashouf, R.* ; Mohammadi, A.* ; Nikkhoo, B.* ; Shokoohizadeh, L.* ; Khan Mirzaei, M. ; Alikhani, M.Y.* ; Sheikhesmaili, F.* ; Khodaei, H.*

Investigating the expression of anti/pro-inflammatory cytokines in the pathogenesis and treatment of ulcerative colitis and its association with serum level of vitamin D.

Sci. Rep. 15:7569 (2025)

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Ulcerative colitis is an idiopathic gastrointestinal disease described by chronic inflammation of the digestive system. Cytokines may be responsible for immunopathogenesis, mucosal and tissue damage, and even treatment response. In addition to its role in calcium and phosphorus homeostasis and bone health, vitamin D is an immunomodulatory and anti-inflammatory agent. Understanding the role of cytokines may lead to improving the pathogenesis and treatment of this disease, therefore we aimed to investigate the relative gene expression of pro- and anti-inflammatory cytokines in biopsy samples taken from the affected area in the colon of ulcerative colitis patients and its association with serum vitamin D levels. A total of 47 ulcerative colitis patients were enrolled in this case-control study. The case group consisted of 23 patients with treatment-resistant ulcerative colitis, and the control group consisted of 24 ulcerative colitis patients responding to routine treatment. Serum vitamin D levels were measured by ELISA method. Real-time PCR was employed to quantify the relative expression of pro- and anti-inflammatory cytokines in colon biopsy samples from case and control groups. The pro-inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, IL-17 A, and IL-33, while the anti-inflammatory cytokines were IL-10, IL-35, and TGF-β. Data are showed as mean ± standard deviation (SD), and p values < 0.05 were considered statistically significant. The mean age of the control group was 45.88 ± 18.51 years, while that of the case group was 41.30 ± 13.01 years. The relative gene expression of TNF-α, IFN-γ, IL-1β, IL-6, IL-8, IL-17 A, IL-33, TGF-β, IL-10, and IL-35, in the case and control groups did not exhibit statistically significant differences (p > 0.05). However, the gene expression levels of the principal pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were elevated in treatment-resistant patients compared to patients who responded to treatments. No correlation was observed between serum vitamin D levels and the gene expression of pro- and anti-inflammatory cytokines (p > 0.05). The present study did not identify a statistically significant correlation between the expression of pro- or anti-inflammatory cytokines and treatment response. Therefore, routine treatments had no effect on the expression of these cytokines in treatment-resistant patients. Additionally, serum vitamin D levels were not related to the relative expression of pro- and anti-inflammatory cytokines in the affected area of the colon of these patients. Despite the need for further research on the protective and pathological roles of cytokines and vitamin D, regular screening and early and complementary treatment may be beneficial in reducing inflammatory symptoms in these patients.

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