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Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis

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Abstract

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016–December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010–1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.

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Acknowledgments

A special thank-you to the Director General of Health Malaysia, Ministry of Health Malaysia, for his permission to publish this article and the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, for the facilities and technical support provided.

Funding

This study was funded by the Ministry of Higher Education Malaysia through the Long-Term Research Grant Scheme (LRGS) (UPM/700-2/1/LRGS/5526402).

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Authors and Affiliations

  1. Department of Medical Laboratory Technology, Faculty of Health Sciences, Universiti Teknologi MARA Cawangan Selangor, Kampus Puncak Alam, 42300, Bandar Puncak Alam, Selangor, Malaysia

    Wan Shahriman Yushdie Wan Yusoff

  2. Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia

    Wan Shahriman Yushdie Wan Yusoff, Zamberi Sekawi, Niazlin Mohd Taib, Leslie Thian Lung Than & Syafinaz Amin Nordin

  3. Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), 43400, Serdang, Selangor, Malaysia

    Maha Abdullah

  4. Infectious Disease Research Centre, Bacteriology Unit, Institute for Medical Research, Ministry of Health Malaysia, 50588, Kuala Lumpur, Malaysia

    Fairuz Amran

  5. Infectious Diseases Unit, Internal Medicine Department, Universiti Teknologi MARA, 47000, Sungai Buloh, Malaysia

    Muhammad Yazli Yuhana

  6. Department of Life Sciences, International Medical University, Jalan Jalil Perkasa 19, Taman Esplanade, 57000, Kuala Lumpur, Malaysia

    Ivan Kok Seng Yap

  7. Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Anim Md. Shah

  8. Clinical Unit, bioMérieux, 3 route de Port Michaud, 38390, La Balme-les-Grottes, France

    Alex van Belkum

Authors
  1. Wan Shahriman Yushdie Wan Yusoff
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  2. Maha Abdullah
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  3. Zamberi Sekawi
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  4. Fairuz Amran
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  5. Muhammad Yazli Yuhana
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  7. Ivan Kok Seng Yap
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  8. Leslie Thian Lung Than
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  9. Anim Md. Shah
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  10. Alex van Belkum
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  11. Syafinaz Amin Nordin
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Contributions

SAN, MA, and ZS were involved in the conception and design of the study. WSY performed the study, analyzed data, and drafted the manuscript. AvB substantially revised the analyses and manuscript. MYY, AMS, and NMT provided clinical data and sample. LT, IK, and FA contributed intellectual content to the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Syafinaz Amin Nordin.

Ethics declarations

Ethical approval and consent to participate

Samples were collected from study participants after they have given their written informed consent. Ethical approval for the study was obtained from the Medical Research and Ethics Committee, Ministry of Health Malaysia (NMRR (National Medical Research Register)-15-2148-27536 and NMRR-15-756-25320).

Informed consent

Written informed consent was obtained from the study participants for publication of their individual details in this manuscript.

Conflict of interest

The authors declare that they have no competing interests.

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Wan Yusoff, W.S.Y., Abdullah, M., Sekawi, Z. et al. Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis. Eur J Clin Microbiol Infect Dis 38, 2349–2353 (2019). https://doi.org/10.1007/s10096-019-03699-5

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  • DOI: https://doi.org/10.1007/s10096-019-03699-5

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