IL-40 levels in treatment-naive and methotrexate-treated rheumatoid arthritis patients

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Oğuzman H., Pekdiker M.

Turkish Journal of Medical Sciences, cilt.55, sa.3, ss.658-665, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 55 Sayı: 3
  • Basım Tarihi: 2025
  • Doi Numarası: 10.55730/1300-0144.6013
  • Dergi Adı: Turkish Journal of Medical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, MEDLINE, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.658-665
  • Anahtar Kelimeler: cytokines, interleukin-4, Interleukin-40, methotrexate, transforming growth factor beta-1, tumor necrosis factor-alpha
  • Hatay Mustafa Kemal Üniversitesi Adresli: Evet

Özet

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by persistent inflammation and progressive damage to the joints. In this study, it was aimed to explore the role of interleukin (IL)-40, a newly discovered cytokine, in the pathogenesis of RA. We also aimed to investigate the relationship between IL-40 and other cytokines such as IL-4, transforming growth factor (TGF)-β1 and tumor necrosis factor (TNF)-α.

Materials and methods: This single-center, cross-sectional study included 87 participants divided into three groups: healthy controls (n = 29), newly diagnosed RA patients (n = 29), and RA patients with remission under methotrexate (MTX) monotherapy (n = 29). Serum samples were collected and analyzed for IL-40, IL-4, TGF-β1 and TNF-α levels using ELISA. Disease activity score, presence of autoantibodies and other relevant clinical data were obtained from hospital electronic records.

Results: Elevated IL-40 levels were found in the newly diagnosed RA patients and in those treated with MTX compared to the control group (p < 0.001). Logistic regression analysis confirmed IL-40 as an independent predictor in the newly diagnosed (OR = 1.023, 95% CI: 1.010–1.035, p = 0.002) and RA MTX-treated patients (OR = 1.023, 95% CI: 1.011–1.036, p < 0.001). IL-40 levels remained unchanged in the newly diagnosed RA group compared to RA patients in the MTX-treated group. In the dual-seropositive patients, TGF-β1 was lower in the MTX-treated RA patients compared to the naive patients (p = 0.013) and in the dual-seronegative patients, TNF-α was decreased in the MTX-treated RA patients in comparison to naive patients (p = 0.043).

Conclusion: This study demonstrates that IL-40 levels are elevated in RA patients and highlights its potential role in RA. The fact that IL-40 levels did not change despite the antiinflammatory effects of MTX suggests that IL-40 is involved in immunological pathways that are less responsive to treatment.