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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Research

Sustained interleukin-10 delivery reduces inflammation and improves motor function after spinal cord injury

Authors: Daniel J. Hellenbrand, Kaitlyn A. Reichl, Benjamin J. Travis, Mallory E. Filipp, Andrew S. Khalil, Domenic J. Pulito, Ashley V. Gavigan, Elizabeth R. Maginot, Mitchell T. Arnold, Alexander G. Adler, William L. Murphy, Amgad S. Hanna

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Background

The anti-inflammatory cytokine interleukin-10 (IL-10) has been explored previously as a treatment method for spinal cord injury (SCI) due to its ability to attenuate pro-inflammatory cytokines and reduce apoptosis. Primary limitations when using systemic injections of IL-10 are that it is rapidly cleared from the injury site and that it does not cross the blood–spinal cord barrier.

Objective

Here, mineral-coated microparticles (MCMs) were used to obtain a local sustained delivery of IL-10 directly into the injury site after SCI.

Methods

Female Sprague-Dawley rats were contused at T10 and treated with either an intraperitoneal injection of IL-10, an intramedullary injection of IL-10, or MCMs bound with IL-10 (MCMs+IL-10). After treatment, cytokine levels were measured in the spinal cord, functional testing and electrophysiology were performed, axon tracers were injected into the brainstem and motor cortex, macrophage levels were counted using flow cytometry and immunohistochemistry, and lesion size was measured.

Results

When treated with MCMs+IL-10, IL-10 was significantly elevated in the injury site and inflammatory cytokines were significantly suppressed, prompting significantly less cells expressing antigens characteristic of inflammatory macrophages and significantly more cells expressing antigens characteristic of earlier stage anti-inflammatory macrophages. Significantly more axons were preserved within the rubrospinal and reticulospinal tracts through the injury site when treated with MCMs+IL-10; however, there was no significant difference in corticospinal tract axons preserved, regardless of treatment group. The rats treated with MCMs+IL-10 were the only group with a significantly higher functional score compared to injured controls 28 days post-contusion.

Conclusion

These data demonstrate that MCMs can effectively deliver biologically active IL-10 for an extended period of time altering macrophage phenotype and aiding in functional recovery after SCI.
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Metadata
Title
Sustained interleukin-10 delivery reduces inflammation and improves motor function after spinal cord injury
Authors
Daniel J. Hellenbrand
Kaitlyn A. Reichl
Benjamin J. Travis
Mallory E. Filipp
Andrew S. Khalil
Domenic J. Pulito
Ashley V. Gavigan
Elizabeth R. Maginot
Mitchell T. Arnold
Alexander G. Adler
William L. Murphy
Amgad S. Hanna
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1479-3

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