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

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

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.

Keywords: acute ischemic brain injury; cytokine; interleukin-37; post-stroke inflammation; pro-inflammatory responses; stroke.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Serum IL-37 level in acute…
Figure 1. Serum IL-37 level in acute stroke patients at the time of admission (blue bars) and after 24 hours.
IL-37: Interleukin-37
Figure 2. Urine IL-37 level in acute…
Figure 2. Urine IL-37 level in acute stroke patients at the time of admission (blue bars) and after 24 hours.
IL-37: Interleukin-37

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