AUTHOR=Zuaiter Mohammad , Axelrod Jonathan H. , Pizov Galina , Gofrit Ofer N. 

TITLE=Hyper-Interleukin-6 Protects Against Renal Ischemic-Reperfusion Injury—A Mouse Model

JOURNAL=Frontiers in Surgery

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2021.605675

DOI=10.3389/fsurg.2021.605675

ISSN=2296-875X

ABSTRACT=<p><bold>Background:</bold> Most of the ischemia-reperfusion injury (IR-I) occurs during reperfusion and is mediated by the immune system. In this study we determined whether immunomodulation with hyper-Interleukin-6 (a recombinant designer cytokine composed of interleukin-6 linked to its soluble receptor) is protective against IR-I in mice kidneys.</p><p><bold>Methods:</bold> Hyper-Interleukin-6 (HIL-6) was administered by <italic>in vivo</italic> plasmid DNA transfection to 10 male mice. Twenty-four hours later, unilateral nephrectomy was done. IR-I immediately followed by closure of the remaining kidney vascular pedicle for 40 min. Seven mice transfected with non-coding control plasmid served as the control group. The functional and morphological effects of IR-I and its effect on mice longevity were explored. This was done by serial blood tests and by histopathology done upon sacrifice of the animals at post-operative day 7.</p><p><bold>Findings:</bold> Mice pretreated with HIL-6 had a mean creatinine level at post-operative day 1 of 35.45 ± 4.03 μmol/l and mean Urea level was 14.18 ± 2.69 mmol/l, whereas mean creatinine was 89.33 ± 69.27 μmol/l (<italic>P</italic> = <italic>0.025</italic>), and mean urea was 38.17 ± 20.77 mmol/l <italic>(P</italic> = <italic>0.0024</italic>) in the control group. Histological changes in the control group included inflammatory infiltration, tubular damage, and architectural distortion. These were not seen in the treatment group. Seven days post-operatively the survival rate of treated mice was 100% compared to 50% in the control group (<italic>P</italic> = <italic>0.015</italic>).</p><p><bold>Interpretation:</bold> In this single kidney mouse model, pretreatment with HIL-6 administration effectively protected against IR-I both morphologically and functionally. Further studies are needed to better understand the mechanism and feasibility of using this immunomodulator.</p>