Role of Interleukin-17 And Interleukin-35 In the Pathophysiology of Respiratory Infections Caused by Multidrug-Resistant Pseudomonas Aeruginosa

Authors

  • Shahad Saad Mohammed Community Health Technologies Department, Babylon Technical Institute, Al-Furat Al-Awsat Technical University, 51015 Babylon, Iraq

Keywords:

IL-17, IL-35, respiratory infections, MDR Pseudomonas aeruginosa

Abstract

Aims: The objective of this study was to assess the IL-17 and IL-35 mediated immune response of patients with respiratory infections attributable to highly resistant (MDR) Pseudomonas aeruginosa and to determine the possible role of these interleukins as biomarkers for severity of disease and clinical outcomes.

Methods and Materials: This cross-sectional study was carried out on 58 patients infected with infection with MDR P. aeruginosa respiratory tract infections in Al-Hussein Teaching Hospital, Karbala, Iraq, from August/2024 to February/2025. Abstract Background Clinical data including the severity of the disease ICU admission need for mechanical ventilation Corticosteroids use and outcomes after 3 weeks were recorded. Inflammatory markers (CRP, procalcitonin, blood cell counts), as well as serum levels of IL-17 and IL-35 were evaluated with ELISA.

Results: The results showed that IL-17 was significantly increased in patients with higher degrees of disease severity, from 56.6±9.3pg/mL in mild disease to 72.4±13.2pg/mL in severe disease (p=0.005). Moreover, higher IL-17 was significantly associated with ICU admission, mechanical ventilation requirement and poor outcomes, including mortality (75.2±13.7pg/mL). In contrast, IL-35 levels were inversely associated with disease severity, falling from 52.3±9.2pg/mL in mild disease to 42.5±7.9pg/mL in severe disease (p=0.008). Low IL-35 levels were found in patients who died (41.2±7.7pg/mL) and high IL-35 levels were found in patients with better outcome. Oxygen saturation and lymphocyte counts also presented with significantly negative correlations with IL-17, whilst IL-35 had significantly positive correlations with oxygen saturation.

Conclusion: The contrasting behaviors of IL-17 and IL-35 suggest a dynamic interplay between pro-inflammatory and anti-inflammatory responses in MDR P. aeruginosa infections. Elevated IL-17 is a marker of increased inflammation and disease severity, while IL-35 may exert protective, regulatory effects. The combined measurement of these cytokines offers promising diagnostic and prognostic value and may inform personalized management strategies for critically ill patients with MDR infections. Further research is recommended to explore their potential as therapeutic targets.

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

Al Hassani, S. A., Karim, A. S., & Mahdi, Y. H. (2023). Serum interleukin-17 levels in ventilator-associated pneumonia due to Pseudomonas aeruginosa. Iraqi Journal of Medical Sciences, 21(4), 215–223.

Al-Mayahie, S. M. (2019). Multidrug-resistant Pseudomonas aeruginosa in Iraq: A growing concern. Journal of Infection in Developing Countries, 13(3), 205–211.

Al Rubaye, L. H., Ahmed, H. A., & Basim, Y. M. (2024). Outbreak of carbapenem-resistant Pseudomonas aeruginosa in Iraqi ICU settings. Middle East Journal of Infectious Diseases, 12(1), 45–53.

Basseti, M., Righi, E., Carnelutti, A., Mercurio, S., & Viaggi, B. (2018). Clinical challenges of Pseudomonas aeruginosa. Infection and Drug Resistance, 11, 167–181.

Caidi, H., Shivam, A., & Henderson, J. P. (2020). Role of IL-17 in bacterial pneumonia: neutrophil recruitment and host defense. Journal of Infectious Diseases, 221(8), 1206–1215.

Chen, K., Kolls, J. K. (2019). Interluekin-17A (IL-17A). Gene, 710, 143-148.

Chung, K. H., Agrawal, A., & Koetzner, C. A. (2014). IL-17 and acute lung inflammation: balancing protection and pathology. American Journal of Respiratory and Critical Care Medicine, 189(12), 1456–1467.

Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., ... & Vignali, D. A. (2010). The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature, 450(7169), 566–569.

Gaffen, S. L., Jain, R., Garg, A. V., & Cua, D. J. (2014). The IL-23–IL-17 immune axis: from discovery to potential therapeutic targeting. Nature Reviews Immunology, 14(8), 585–600.

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

Hadi, H. S., Shubar, S. N. A., Jaffar, A. M., & Al-fahham, A. A. (2024). Structure and physiological significance of IL-17: A review article. International Journal of Health & Medical Research, 3(9), 666–669. https://doi.org/10.58806/ijhmr.2024.v3i09n03

Hassan, Z. et al. (2021). Antimicrobial resistance and mortality in MENA region: a systematic review. Clinical Microbiology and Infection, 27(5), 627–635.

Jepson, M. A., Clark, D. C., & Lowe, D. M. (2008). IL-17 mediated neutrophil recruitment in bacterial pneumonia. Infection and Immunity, 76(10), 4305–4311.

Kalil, A. C., Metersky, M. L., Klompas, M., Muscedere, J., Sweeney, D. A., Palmer, L. B., ... & Brozek, J. L. (2016). Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines. Clinical Infectious Diseases, 63(5), e61–e111.

Moradali, M. F., Ghods, S., & Rehm, B. H. A. (2017). Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Frontiers in Cellular and Infection Microbiology, 7, 39.

Mtsher, A. M., 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

Niedbala, W., Wei, X. Q., Cai, B., Hueber, A. J., Leung, B. P., McInnes, I. B., & Liew, F. Y. (2007). IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. European Journal of Immunology, 37(11), 3021–3029.

Raffetseder, J., Philogene, L. C., & Lynch, J. P. (2019). Innate and adaptive immune responses in Pseudomonas aeruginosa respiratory infection. Clinical Microbiology Reviews, 32(3), e00078-18.

Rodríguez-Hernández, J. M., García-Ríos, D., Cordero, E., & Pachón, J. (2022). Epidemiology and management of multidrug-resistant Pseudomonas aeruginosa in intensive care units. Current Opinion in Infectious Diseases, 35(6), 490–496.

Shen, Y., Wang, H., Xu, Y., & Liu, Y. (2021). IL-35 mitigates inflammation and lung injury in bacterial pneumonia by promoting regulatory T cells. International Immunopharmacology, 93, 107390.

Smith, J. D., Rahman, R., & Patel, N. (2020). IL-35 in cystic fibrosis patients with bacterial pneumonia. Pediatric Pulmonology, 55(6), 1403–1410.

Stockinger, B., & Omenetti, S. (2017). The dichotomous nature of T helper 17 cells. Nature Reviews Immunology, 17(9), 535–544.

Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., ... & Ouellette, M. (2018). Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, 18(3), 318–327.

Tumbarello, M., Trecarichi, E. M., & Losito, A. (2019). MDR Pseudomonas aeruginosa in hospital-acquired pneumonia: clinical outcomes. British Journal of Clinical Infectious Diseases, 41(3), 700–708.

Wirtz, S., Neufert, C., Weigmann, B., & Neurath, M. F. (2014). Mechanisms of IL-35 mediated inflammation regulation. Immunology Letters, 158(1–2), 109–117.

Zhang, R., Li, X., & Yu, Z. (2021). IL-35 in murine bacterial pneumonia: balancing immunity and pathology. Frontiers in Immunology, 12, 689726.

Zhu, Q., Zhao, Y., & Wang, H. (2022). Cytokine balance in respiratory infections: IL-17 vs IL-35. Cytokine, 149, 155728.

Published

2025-11-25