Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury
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01.12.2021 |
Yates A.G.
Jogia T.
Gillespie E.R.
Couch Y.
Ruitenberg M.J.
Anthony D.C.
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Journal of Neuroinflammation |
10.1186/s12974-020-02050-6 |
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© 2021, The Author(s). Background: The acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord. Methods: Adult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate. Results: SCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself. Conclusions: Our data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.
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Presepsin - A new biological marker for sepsis diagnosing and monitoring the effect of treatment
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01.01.2018 |
Kukes V.
Marinin V.
Olefir Y.
Shih E.
Prokofiev A.
Grapov D.
Verdieva D.
Rumyantsev N.
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Medical News of North Caucasus |
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© 2018 Stavropol State Medical University. All Rights Reserved. A retrospective analysis included 31 patients aged 23 to 78 years with the signs of SIRS from the departments of therapy, pulmonology and the intensive care unit (ICU) with the diagnosis of severe community-acquired or hospital-acquired pneumonia. The plasma level of presepsin protein was assessed using the Pathfast immunochemiluminescence analyzer (Japan). It was revealed that at hospitalization, the level of PSP was significantly higher in patients with SIRS than in healthy individuals. Patients with the diagnosis of sepsis (later confirmed by hemoculture) showed a higher concentration during hospitalization and at all subsequent time points of the study, which characterizes presepsin as a marker of sepsis in difficult clinical settings.
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