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Journals / Dünya Sağlık ve Tabiat Bilimleri Dergisi / 2026 / Cilt: 6 Sayı: 1

Evaluation of The Relationship Between Serum IL-33 Levels and Pulmonary Fibrosis in Severe COVID-19 Patients

Ağır COVID-19 Hastalarında Serum IL-33 Düzeylerinin Pulmoner Fibrozis ile İlişkisinin Değerlendirilmesi

Çiğdem Damla Deniz(konya şehir hastanesi)0000-0002-6052-4645
Fatih Yücel(Konya Şehir Hastanesi)0000-0002-1947-5853
Hasan Şenay(Konya Şehir Hastanesi)0000-0001-9956-1788
Fatma Kacar(Medova Hastanesi)0000-0001-7013-6403
Mehmet Sinan İyisoy(NECMETTİN ERBAKAN ÜNİVERSİTESİ, MERAM TIP FAKÜLTESİ, MERAM TIP PR.)0000-0001-5895-9984
Nahide Baran(konya cihanbeyli devlet hastanesi)0000-0001-6387-423X
Betül Kozanhan(konya şehir hastanesi)0000-0002-5097-9291
Mehmet Eryılmaz(konya şehir hastanesi)0000-0002-5280-3943
Mehmet Koc(NECMETTİN ERBAKAN ÜNİVERSİTESİ, MERAM TIP FAKÜLTESİ, MERAM TIP PR.)0000-0002-1433-8403
Pages
1–13
Publication Date
2023-06-19
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

According to the results of the ROC analysis, the sensitivity for IL-33 was 97%, the specificity was 86%, and the AUC value was 1.97.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:The aim of this study is to investigate the predictive value of IL-33 in the development of pulmonary fibrosis in patients diagnosed with COVID-19 and followed up.
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Key Findings & Data:Our study was carried out on patients with a definitive diagnosis of COVID-19 who were followed up in the Intensive Care Unit of Konya Training and Research Hospital.
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Conclusion & Impact:According to the results of the ROC analysis, the sensitivity for IL-33 was 97%, the specificity was 86%, and the AUC value was 1.97.
🔬Design:Klinik Araştırma
📍Scope:Comprehensive Sample
⚙️Variables:COVID-19 · IL-33 · akciğer fibrozisi

Abstract

The aim of this study is to investigate the predictive value of IL-33 in the development of pulmonary fibrosis in patients diagnosed with COVID-19 and followed up. Our study was carried out on patients with a definitive diagnosis of COVID-19 who were followed up in the Intensive Care Unit of Konya Training and Research Hospital. ELISA method was used to measure IL-33 concentrations. White blood cell (WBC), hemoglobin value, platelet (PLT) and lymphocyte (LNF) counts of the patients; coagulation-related parameters such as D-dimer and fibrinogen; C-reactive protein (CRP), albumin (Alb), uric acid, ferritin (FER) and lactate and pO2 results from arterial blood gases were included in the study. Correlations of cytokine levels with clinical, biochemical and radiographic data were analyzed. We found that COVID-19 patients with severe disease had a significantly higher serum IL-33 concentration. A moderate positive correlation was found between serum values of IL-33 and CRP, CRP/Alb ratio and uric acid. In the presence of subpleural band, IL-33 levels were found to be significantly higher, and FER and PLT levels were significantly lower. In the presence of fibrotic stripe, IL-33 levels were significantly higher; WBC, PLT and PLT/LNF ratios were found to be significantly lower. According to the results of the ROC analysis, the sensitivity for IL-33 was 97%, the specificity was 86%, and the AUC value was 1.97. IL-33 is associated with some radiological and laboratory parameters of COVID-19 and is a promising marker in COVID-19 and may also represent a therapeutic target.

Özet

Bu çalışmanın amacı, COVID-19 tanısı alarak, takip edilen hastalarda, pulmoner fibrozis gelişiminde IL-33’ün prediktif değerini araştırmaktır. Çalışmamız Konya Eğitim ve Araştırma Hastanesi, Yoğun Bakım Ünitesinde takip edilmiş COVID-19 kesin tanılı hastalar üzerinde yapılmıştır. IL-33 konsantrasyonlarını ölçmek için ELISA yöntemi kullanılmıştır. Hastaların, beyaz kan hücresi (WBC), hemoglobin değeri, trombosit (PLT) ve lenfosit (LNF) sayıları; D-dimer ve fibrinojen gibi koagülasyon ile ilişkili parametreleri; C-reaktif protein (CRP), albümin (Alb), ürik asit, ferritin (FER) ve arter kan gazlarından laktat ve pO2 sonuçları çalışmaya dahil edilmiştir. Sitokin düzeyleri ile klinik, biyokimyasal, radyografik verilerin korelasyonları analiz edilmiştir. Şiddetli hastalığı olan COVID-19 hastalarında önemli ölçüde daha yüksek serum IL-33 konsantrasyonu olduğu bulunmuştur. IL-33'ün serum değerleri ile CRP, CRP/Alb oranı ve ürik asit arasında orta düzeyde pozitif korelasyon saptanmıştır. Subplevral bant varlığında IL-33 düzeylerinin anlamlı düzeyde yüksek, FER ve PLT düzeylerinin anlamlı düzeyde düşük olduğu görülmüştür. Fibrotik şerit varlığında IL-33 düzeylerinin anlamlı düzeyde yüksek; WBC, PLT ve PLT/LNF oranının anlamlı düzeyde düşük olduğu görülmüştür. ROC analizi sonuçlarına göre IL-33 için sensitivite %97, spesifisite %86 ve AUC değeri 1,97 olarak bulunmuştur. IL-33, COVID-19'un bazı radyolojik ve laboratuvar parametreleriyle ilişkili ve COVID-19'da umut verici bir belirteç olarak belirlendiği için terapötik bir hedefi temsil edebilir.

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Cite This Article

Deniz, Ç. D., Yücel, F., Şenay, H., Kacar, F., İyisoy, M. S., Baran, N., Kozanhan, B., Eryılmaz, M., Koc, M. (2023). Evaluation of The Relationship Between Serum IL-33 Levels and Pulmonary Fibrosis in Severe COVID-19 Patients. Dünya Sağlık ve Tabiat Bilimleri Dergisi, Cilt: 6 Sayı: 1, 1–13. https://ajindex.com/articles/1633148

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References (46)

  1. Atalay, E., Çelik, S., & Kahraman, İ. (2021). Investigation of the Effect of COVID-19 on Kidney Functions. Dünya Sağlık ve Tabiat Bilimleri Dergisi, 4(2), 75-79.
  2. Beltrán, C. J., Núñez, L. E., Díaz-Jiménez, D., Farfan, N., Candia, E., Heine, C. … Hermoso, M. A. (2010). Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis, 16(7), 1097-1107. https://doi.org/10.1002/ibd.21175
  3. Butt, M. U., & Jabri, A. (2019). Azithromycin-Induced Thrombocytopenia: A Rare Etiology of Drug-Induced Immune Thrombocytopenia. Case Reports in Medicine, 2019, 1(3). 6109831. https://doi.org/10.1155/2019/6109831
  4. Carriere, V., Roussel, L., Ortega, N., Lacorre, D. A., Americh, L., Aguilar, L. … Girard, J. P. (2007). IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A, 104(1), 282-287. https://doi.org/10.1073/pnas.0606854104
  5. Cayrol, C., & Girard, J. P. (2018). Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunological reviews, 281(1), 154-168. https://doi.org/10.1111/imr.12619
  6. Channappanavar, R., & Perlman, S. (2017). Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol, 39(5), 529-539. https://doi.org/10.1007/s00281-017-0629-x
  7. Demir, D., Öcal, F., Abanoz, M., & Dermenci, H. (2014). A case of thrombocytopenia associated with the use of hydroxychloroquine following open heart surgery. Int J Surg Case Rep, 5(12), 1282-1284. https://doi.org/10.1016/j.ijscr.2014.11.052
  8. Drake LY, Kita H. (2017). IL-33: biological properties, functions, and roles in airway disease. Immunol Rev., 278(1):173-184. https://doi.org/10.1111/imr.12552.
  9. Fan, B. E., Chong, V. C. L., Chan, S. S. W., Lim, G. H., Lim, K. G. E., Tan, G. B. … Ong, K. H. (2020). Hematologic parameters in patients with COVID-19 infection. Am J Hematol, 95(6), E131-e134. https://doi.org/10.1002/ajh.25774
  10. Gomez-Cadena, A., Spehner, L., Kroemer, M., Khelil, M. B., Bouiller, K., Verdeil, G. … Jandus, C. (2021). Severe COVID-19 patients exhibit an ILC2 NKG2D(+) population in their impaired ILC compartment. Cell Mol Immunol, 18(2), 484-486. https://doi.org/10.1038/s41423-020-00596-2
  11. Güçlü, E., & Kocayiğit, H. (2020). Effect of COVID-19 on platelet count and its indices. Revista da Associação Médica Brasileira, 66(8), 1122-1127. https://doi.org/10.1590/1806-9282.66.8.1122
  12. Hasan, A., Al-Ghimlas, F., Warsame, S., Al-Hubail, A., Ahmad, R., Bennakhi, A. … Dermime, S. (2014). IL-33 is negatively associated with the BMI and confers a protective lipid/metabolic profile in non-diabetic but not diabetic subjects. BMC Immunol, 15, 19. https://doi.org/10.1186/1471-2172-15-19
  13. Keleş, G. T., & Bozkurt, İ. (2021). COVID-19 Hastalığı Tanı ve Tedavisinde Kullanılan Laboratuvar Testleri. Celal Bayar Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 8(2), 380-387.
  14. Kritas, S. K., Ronconi, G., Caraffa, A., Gallenga, C. E., Ross, R., & Conti, P. (2020). Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents, 34(1), 9-14. https://doi.org/10.23812/20-Editorial-Kritas
  15. Lee, J. S., Seppanen, E., Patel, J., Rodero, M. P., & Khosrotehrani, K. (2016). ST2 receptor invalidation maintains wound inflammation, delays healing and increases fibrosis. Exp Dermatol, 25(1), 71-74. https://doi.org/10.1111/exd.12833
  16. Lee, J. U., Chang, H. S., Lee, H. J., Jung, C. A., Bae, D. J., Song, H. J. … Park, C. S. (2017). Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis. BMC Pulm Med, 17(1), 39. https://doi.org/10.1186/s12890-017-0380-z
  17. Li, D., Guabiraba, R., Besnard, A. G., Komai-Koma, M., Jabir, M. S., Zhang, L. … Xu, D. (2014). IL-33 promotes ST2-dependent lung fibrosis by the induction of alternatively activated macrophages and innate lymphoid cells in mice. J Allergy Clin Immunol, 134(6), 1422-1432.e1411. https://doi.org/10.1016/j.jaci.2014.05.011
  18. Li, G., & Fan, Y. (2020). Coronavirus infections and immune responses. 92(4), 424-432. https://doi.org/10.1002/jmv.25685
  19. Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J. … Amit, I. (2020). Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nature Medicine, 26, 842-844. https://doi.org/10.1038/s41591-020-0901-9
  20. Liew, F. Y., Girard, J. P., & Turnquist, H. R. (2016). Interleukin-33 in health and disease. Nat Rev Immunol, 16(11), 676-689. https://doi.org/10.1038/nri.2016.95
  21. Liew, F. Y., Pitman, N. I., & McInnes, I. B. (2010). Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol, 10(2), 103-110. https://doi.org/10.1038/nri2692
  22. Lippi, G., Plebani, M., & Henry, B. M. (2020). Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta, 506, 145-148. https://doi.org/10.1016/j.cca.2020.03.022
  23. Luzina, I. G., Kopach, P., Lockatell, V., Kang, P. H., Nagarsekar, A., Burke, A. P. … Atamas, S. P. (2013). Interleukin-33 potentiates bleomycin-induced lung injury. Am J Respir Cell Mol Biol, 49(6), 999-1008. https://doi.org/10.1165/rcmb.2013-0093OC
  24. Manetti, M., Ibba-Manneschi, L., Liakouli, V., Guiducci, S., Milia, A. F., Benelli, G. … Cipriani, P. (2010). The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis. Ann Rheum Dis, 69(3), 598-605. https://doi.org/10.1136/ard.2009.119321
  25. Marvie, P., Lisbonne, M., L'Helgoualc'h, A., Rauch, M., Turlin, B., Preisser, L. … Samson, M. (2010). Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med, 14(6b), 1726-1739. https://doi.org/10.1111/j.1582-4934.2009.00801.x
  26. Matta, B. M., Lott, J. M., Mathews, L. R., Liu, Q., Rosborough, B. R., Blazar, B. R. … Turnquist, H. R. (2014). IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells. J Immunol, 193(8), 4010-4020. https://doi.org/10.4049/jimmunol.1400481
  27. Miller, A. M., Asquith, D. L., Hueber, A. J., Anderson, L. A., Holmes, W. M., McKenzie, A. N. … Liew, F. Y. (2010). Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res, 107(5), 650-658. https://doi.org/10.1161/circresaha.110.218867
  28. Miller, A. M., & Liew, F. Y. (2011). The IL-33/ST2 pathway--A new therapeutic target in cardiovascular disease. Pharmacol Ther, 131(2), 179-186. https://doi.org/10.1016/j.pharmthera.2011.02.005
  29. Miller, A. M., Xu, D., Asquith, D. L., Denby, L., Li, Y., Sattar, N. … Liew, F. Y. (2008). IL-33 reduces the development of atherosclerosis. J Exp Med, 205(2), 339-346. https://doi.org/10.1084/jem.20071868
  30. Moussion, C., Ortega, N., & Girard, J. P. (2008). The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One, 3(10), e3331. https://doi.org/10.1371/journal.pone.0003331
  31. Nishida, A., Andoh, A., Imaeda, H., Inatomi, O., Shiomi, H., & Fujiyama, Y. (2010). Expression of interleukin 1-like cytokine interleukin 33 and its receptor complex (ST2L and IL1RAcP) in human pancreatic myofibroblasts. Gut, 59(4), 531-541. https://doi.org/10.1136/gut.2009.193599
  32. Paules, C. I., Marston, H. D., & Fauci, A. S. (2020). Coronavirus Infections-More Than Just the Common Cold. Jama, 323(8), 707-708. https://doi.org/10.1001/jama.2020.0757
  33. Préfontaine, D., Lajoie-Kadoch, S., Foley, S., Audusseau, S., Olivenstein, R., Halayko, A. J. … Hamid, Q. (2009). Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cells. J Immunol, 183(8), 5094-5103. https://doi.org/10.4049/jimmunol.0802387
  34. Ravanetti, L., Dijkhuis, A., Dekker, T., Sabogal Pineros, Y. S., Ravi, A., Dierdorp, B. S. … Lutter, R. (2019). IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive antiviral immunity. J Allergy Clin Immunol, 143(4), 1355-1370.e1316. https://doi.org/10.1016/j.jaci.2018.08.051
  35. Sakashita, M., Yoshimoto, T., Hirota, T., Harada, M., Okubo, K., Osawa, Y. … Tamari, M. (2008). Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis. Clin Exp Allergy, 38(12), 1875-1881. https://doi.org/10.1111/j.1365-2222.2008.03114.x
  36. Schmitz, J., Owyang, A., Oldham, E., Song, Y., Murphy, E., McClanahan, T. K. … Kastelein, R. A. (2005). IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity, 23(5), 479-490. https://doi.org/10.1016/j.immuni.2005.09.015
  37. Shieh, J. M., Tseng, H. Y., Jung, F., Yang, S. H., & Lin, J. C. (2019). Elevation of IL-6 and IL-33 Levels in Serum Associated with Lung Fibrosis and Skeletal Muscle Wasting in a Bleomycin-Induced Lung Injury Mouse Model. 2019, 7947596. https://doi.org/10.1155/2019/7947596
  38. Xia, J., Zhao, J., Shang, J., Li, M., Zeng, Z., Zhao, J. … Xie, J. (2015). Increased IL-33 expression in chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol, 308(7), L619-627. https://doi.org/10.1152/ajplung.00305.2014
  39. Xiong, Y., Liu, Y., Cao, L., Wang, D., Guo, M., Jiang, A. … Lin, Y. (2020). Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. 9(1), 761-770. https://doi.org/10.1080/22221751.2020.1747363
  40. Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C. … Wang, F. S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 8(4), 420-422. https://doi.org/10.1016/s2213-2600(20)30076-x
  41. Yang, S. H., Lin, J. C., Wu, S. Y., Huang, K. L., Jung, F., Ma, M. C., Wang Hsu, G. S., & Jow, G. M. (2015). Membrane translocation of IL-33 receptor in ventilator induced lung injury. PLoS One, 10(3), e0121391. https://doi.org/10.1371/journal.pone.0121391
  42. Yang, X., Yang, Q., Wang, Y., Wu, Y., Xu, J., Yu, Y. … Shang, Y. (2020). Thrombocytopenia and its association with mortality in patients with COVID-19. J Thromb Haemost, 18(6), 1469-1472. https://doi.org/10.1111/jth.14848
  43. Yoon, S. H., Lee, K. H., Kim, J. Y., Lee, Y. K., Ko, H., Kim, K. H., … Kim, Y. H. (2020). Chest Radiographic and CT Findings of the 2019 novel coronavirus disease (COVID-19): Analysis of nine patients treated in Korea. Korean J Radiol, 21(4), 494-500. https://doi.org/10.3348/kjr.2020.0132
  44. Zaibi, M. S., Kępczyńska, M. A., Harikumar, P., Alomar, S. Y., & Trayhurn, P. (2018). IL-33 stimulates expression of the GPR84 (EX33) fatty acid receptor gene and of cytokine and chemokine genes in human adipocytes. Cytokine, 110, 189-193. https://doi.org/10.1016/j.cyto.2018.05.008
  45. Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W. … Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270-273. https://doi.org/10.1038/s41586-020-2012-7
  46. Zizzo, G., & Cohen, P. L. (2020). Imperfect storm: is interleukin-33 the Achilles heel of COVID-19? Lancet Rheumatol, 2(12), e779-e790. https://doi.org/10.1016/s2665-9913(20)30340-4