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

  • Wan Shahriman Yushdie Wan Yusoff
  • Maha Abdullah
  • Zamberi Sekawi
  • Fairuz Amran
  • Muhammad Yazli Yuhana
  • Niazlin Mohd Taib
  • Ivan Kok Seng Yap
  • Leslie Thian Lung Than
  • Anim Md. Shah
  • Alex van Belkum
  • Syafinaz Amin NordinEmail author
Original Article


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.


Cytokines Leptospirosis Clinical outcome Biomarkers T helper cell Malaysia 



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.

Authors’ 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.

Funding information

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).

Compliance with ethical standards

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wan Shahriman Yushdie Wan Yusoff
    • 1
    • 2
  • Maha Abdullah
    • 3
  • Zamberi Sekawi
    • 2
  • Fairuz Amran
    • 4
  • Muhammad Yazli Yuhana
    • 5
  • Niazlin Mohd Taib
    • 2
  • Ivan Kok Seng Yap
    • 6
  • Leslie Thian Lung Than
    • 2
  • Anim Md. Shah
    • 7
  • Alex van Belkum
    • 8
  • Syafinaz Amin Nordin
    • 2
    Email author
  1. 1.Department of Medical Laboratory Technology, Faculty of Health SciencesUniversiti Teknologi MARA Cawangan SelangorBandar Puncak AlamMalaysia
  2. 2.Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health SciencesUniversiti Putra Malaysia (UPM)SerdangMalaysia
  3. 3.Department of Pathology, Faculty of Medicine and Health SciencesUniversiti Putra Malaysia (UPM)SerdangMalaysia
  4. 4.Infectious Disease Research Centre, Bacteriology UnitInstitute for Medical Research, Ministry of Health MalaysiaKuala LumpurMalaysia
  5. 5.Infectious Diseases Unit, Internal Medicine DepartmentUniversiti Teknologi MARASungai BulohMalaysia
  6. 6.Department of Life SciencesInternational Medical UniversityKuala LumpurMalaysia
  7. 7.Department of Medicine, Faculty of Medicine and Health SciencesUniversiti Putra MalaysiaSerdangMalaysia
  8. 8.Clinical UnitbioMérieuxLa Balme-les-GrottesFrance

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