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Original article
peer-reviewed

Measurement of Elevated IL-37 Levels in Acute Ischemic Brain Injury: A Cross-sectional Pilot Study



Abstract

Interleukin (IL)-37 is a new member of the IL-1 cytokine family with a defined role as a negative feedback inhibitor of proinflammatory responses. IL-37 has yet to be evaluated in non-immune-mediated neurological diseases, such as ischemic or hemorrhagic strokes. This study aimed to measure urine and serum IL-37 levels in patients with ischemic stroke. Twelve patients consented for our study. Two sets of serum and urine samples were obtained and analyzed, one upon admission to the hospital and the second the next morning. The trends in serum levels of IL- 37 in six stroke patients and the trends in the urine levels of eight stroke patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Our pilot study showed IL-37 levels in urine in stroke patients ranging between 210 and 4,534. Serum IL-37 levels were in the range of 44 - 5,235 in patients with ischemic stroke. Three patients who presented within three hours of stroke onset had IL-37 serum levels of 2,655 pg/ml, 3,517 pg/ml, and 5,235 pg/ml, respectively. In all others, it ranged much less than that, with the trend of delayed presentation giving lower IL-37 levels. The study shows a rather stable early elevation of serum IL-37 levels post-ischemic stroke. IL-37 plays a certain role in mediating post-stroke inflammation with a significant increase in serum levels of this novel cytokine observed in ischemic stroke patients. Further large-scale studies need to be done to establish its definite role. A prospective "CRISP" trial is registered with the ClinicalTrials.gov (Identifier: NCT03297827) to determine the role of IL-37 in modulating post-stroke inflammation.



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Original article
peer-reviewed

Measurement of Elevated IL-37 Levels in Acute Ischemic Brain Injury: A Cross-sectional Pilot Study


Author Information

Atif Zafar

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Asad Ikram Corresponding Author

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Dinesh V. Jillella

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Duraisamy Kempuraj

Neurology, School of Medicine, University of Missouri, Columbia, Mo, Usa

Mohammad Moshahid Khan

Neurology, University of Tennessee Health Science Center Memphis

Saif Bushnaq

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Harold Adam

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Santiago Ortega-Gutierrez

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Radiology, University of Iowa Hospitals and Clinics, , Iowa City, Ia, Usa

Neurosurgery, University of Iowa Hospitals and Clinics, , Iowa City, Ia, Usa

Syed A. Quadri

Neurosurgery, California Institute of Neurosciences

Mudassir Farooqui

Neurosciences, Oklahoma

Asgar Zaheer

Neurology, University of Missouri

Enrique C. Leira

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. Institutional Review Board, University of Iowa Hospitals and Clinics, Iowa City, IA, USA issued approval 201302703. Dr. Zafar got the IRB approval (IRB # 201302703) for this pilot project from the "University of Iowa Hospitals and Clinics" and enrolled patients at the University of Iowa Hospitals and Clinics in this pilot project after taking an informed consent when he was affiliated with the University of Iowa Hospitals and Clinics. More recently, Dr. Zafar joined the University of New Mexico and received an approval for a larger-scale study with IRB # 17-315, with him as a "PI" based on the same protocol, and registered the "CRISP" clinical trial (NCT03297827), which is basically the continuation of this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Original article
peer-reviewed

Measurement of Elevated IL-37 Levels in Acute Ischemic Brain Injury: A Cross-sectional Pilot Study


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Original article
peer-reviewed

Measurement of Elevated IL-37 Levels in Acute Ischemic Brain Injury: A Cross-sectional Pilot Study

Atif Zafar">Atif Zafar, Asad Ikram">Asad Ikram , Dinesh V. Jillella">Dinesh V. Jillella, Duraisamy Kempuraj">Duraisamy Kempuraj, Mohammad Moshahid Khan">Mohammad Moshahid Khan, Saif Bushnaq">Saif Bushnaq, Harold Adam">Harold Adam, Santiago Ortega-Gutierrez">Santiago Ortega-Gutierrez, Syed A. Quadri">Syed A. Quadri, Mudassir Farooqui">Mudassir Farooqui, Asgar Zaheer">Asgar Zaheer, Enrique C. Leira">Enrique C. Leira

  • Author Information
    Atif Zafar

    Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

    Asad Ikram Corresponding Author

    Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

    Dinesh V. Jillella

    Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

    Duraisamy Kempuraj

    Neurology, School of Medicine, University of Missouri, Columbia, Mo, Usa

    Mohammad Moshahid Khan

    Neurology, University of Tennessee Health Science Center Memphis

    Saif Bushnaq

    Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

    Harold Adam

    Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

    Santiago Ortega-Gutierrez

    Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

    Radiology, University of Iowa Hospitals and Clinics, , Iowa City, Ia, Usa

    Neurosurgery, University of Iowa Hospitals and Clinics, , Iowa City, Ia, Usa

    Syed A. Quadri

    Neurosurgery, California Institute of Neurosciences

    Mudassir Farooqui

    Neurosciences, Oklahoma

    Asgar Zaheer

    Neurology, University of Missouri

    Enrique C. Leira

    Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: Consent was obtained by all participants in this study. Institutional Review Board, University of Iowa Hospitals and Clinics, Iowa City, IA, USA issued approval 201302703. Dr. Zafar got the IRB approval (IRB # 201302703) for this pilot project from the "University of Iowa Hospitals and Clinics" and enrolled patients at the University of Iowa Hospitals and Clinics in this pilot project after taking an informed consent when he was affiliated with the University of Iowa Hospitals and Clinics. More recently, Dr. Zafar joined the University of New Mexico and received an approval for a larger-scale study with IRB # 17-315, with him as a "PI" based on the same protocol, and registered the "CRISP" clinical trial (NCT03297827), which is basically the continuation of this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements


    Article Information

    Published: October 11, 2017

    DOI

    10.7759/cureus.1767

    Cite this article as:

    Zafar A, Ikram A, Jillella D V, et al. (October 11, 2017) Measurement of Elevated IL-37 Levels in Acute Ischemic Brain Injury: A Cross-sectional Pilot Study. Cureus 9(10): e1767. doi:10.7759/cureus.1767

    Publication history

    Received by Cureus: September 20, 2017
    Peer review began: September 29, 2017
    Peer review concluded: October 09, 2017
    Published: October 11, 2017

    Copyright

    © Copyright 2017
    Zafar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Interleukin (IL)-37 is a new member of the IL-1 cytokine family with a defined role as a negative feedback inhibitor of proinflammatory responses. IL-37 has yet to be evaluated in non-immune-mediated neurological diseases, such as ischemic or hemorrhagic strokes. This study aimed to measure urine and serum IL-37 levels in patients with ischemic stroke. Twelve patients consented for our study. Two sets of serum and urine samples were obtained and analyzed, one upon admission to the hospital and the second the next morning. The trends in serum levels of IL- 37 in six stroke patients and the trends in the urine levels of eight stroke patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Our pilot study showed IL-37 levels in urine in stroke patients ranging between 210 and 4,534. Serum IL-37 levels were in the range of 44 - 5,235 in patients with ischemic stroke. Three patients who presented within three hours of stroke onset had IL-37 serum levels of 2,655 pg/ml, 3,517 pg/ml, and 5,235 pg/ml, respectively. In all others, it ranged much less than that, with the trend of delayed presentation giving lower IL-37 levels. The study shows a rather stable early elevation of serum IL-37 levels post-ischemic stroke. IL-37 plays a certain role in mediating post-stroke inflammation with a significant increase in serum levels of this novel cytokine observed in ischemic stroke patients. Further large-scale studies need to be done to establish its definite role. A prospective "CRISP" trial is registered with the ClinicalTrials.gov (Identifier: NCT03297827) to determine the role of IL-37 in modulating post-stroke inflammation.



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Atif Zafar

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Asad Ikram, M.D., Fellow Physician, Clinical Research Fellow

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

For correspondence:
aikram@salud.unm.edu

Dinesh V. Jillella

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Duraisamy Kempuraj, Ph.D., Assistant Professor

Neurology, School of Medicine, University of Missouri, Columbia, Mo, Usa

Mohammad Moshahid Khan

Neurology, University of Tennessee Health Science Center Memphis

Saif Bushnaq

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Harold Adam

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Santiago Ortega-Gutierrez, M.D., M.Sc.

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Syed A. Quadri

Neurosurgery, California Institute of Neurosciences

Mudassir Farooqui

Neurosciences, Oklahoma

Asgar Zaheer

Neurology, University of Missouri

Enrique C. Leira

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Atif Zafar

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Asad Ikram, M.D., Fellow Physician, Clinical Research Fellow

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

For correspondence:
aikram@salud.unm.edu

Dinesh V. Jillella

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Duraisamy Kempuraj, Ph.D., Assistant Professor

Neurology, School of Medicine, University of Missouri, Columbia, Mo, Usa

Mohammad Moshahid Khan

Neurology, University of Tennessee Health Science Center Memphis

Saif Bushnaq

Cerebrovascular Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA

Harold Adam

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Santiago Ortega-Gutierrez, M.D., M.Sc.

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa

Syed A. Quadri

Neurosurgery, California Institute of Neurosciences

Mudassir Farooqui

Neurosciences, Oklahoma

Asgar Zaheer

Neurology, University of Missouri

Enrique C. Leira

Neurology, University of Iowa Hospitals and Clinics, Iowa City, Ia, Usa