IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury

The prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active fo...

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Main Authors: Easmin Begum, Md Rashel Mahmod, Md Mahbobur Rahman, Fumiko Fukuma, Takeshi Urano, Yuki Fujita
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/1/16
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author Easmin Begum
Md Rashel Mahmod
Md Mahbobur Rahman
Fumiko Fukuma
Takeshi Urano
Yuki Fujita
author_facet Easmin Begum
Md Rashel Mahmod
Md Mahbobur Rahman
Fumiko Fukuma
Takeshi Urano
Yuki Fujita
author_sort Easmin Begum
collection DOAJ
description The prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active form of IL-18. This study evaluated the functional effects of this antibody in a mouse model of SCI. IL-18 expression was significantly upregulated in the spinal cord following injury. In a mouse model of SCI (C57BL/6J strain), mice were administered 150 μg of the anti-IL-18 antibody intraperitoneally. IL-18 inhibition via antibody treatment facilitated motor functional recovery post-injury. This intervention reduced neuronal death, reactive gliosis, microglia/macrophage activation, and neutrophil infiltration. Additionally, IL-18 inhibition lowered the expression of pro-inflammatory factors, such as IL-1β and the M1 microglia/macrophage marker Ccl17, while enhancing the expression of the M2 microglia/macrophage marker Arginase 1. Collectively, our findings demonstrate that IL-18 inhibition promotes motor recovery and facilitates the polarization of M1 microglia/macrophages to the M2 phenotype, thereby fostering a neuroprotective immune microenvironment in mice with SCI.
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spelling doaj-art-4ff88048e92e4162b0cde69c0f2f4b582025-01-24T13:24:52ZengMDPI AGBiomolecules2218-273X2024-12-011511610.3390/biom15010016IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord InjuryEasmin Begum0Md Rashel Mahmod1Md Mahbobur Rahman2Fumiko Fukuma3Takeshi Urano4Yuki Fujita5Department of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanDepartment of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanDepartment of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanDepartment of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanCenter for Vaccines and Therapeutic Antibodies for Emerging Infectious Diseases, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanDepartment of Anatomy and Developmental Biology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo 693-8501, Shimane, JapanThe prognosis of spinal cord injury (SCI) is closely linked to secondary injury processes, predominantly driven by neuroinflammation. Interleukin-18 (IL-18) plays a pivotal role in this inflammatory response. In previous work, we developed an anti-IL-18 antibody capable of neutralizing the active form of IL-18. This study evaluated the functional effects of this antibody in a mouse model of SCI. IL-18 expression was significantly upregulated in the spinal cord following injury. In a mouse model of SCI (C57BL/6J strain), mice were administered 150 μg of the anti-IL-18 antibody intraperitoneally. IL-18 inhibition via antibody treatment facilitated motor functional recovery post-injury. This intervention reduced neuronal death, reactive gliosis, microglia/macrophage activation, and neutrophil infiltration. Additionally, IL-18 inhibition lowered the expression of pro-inflammatory factors, such as IL-1β and the M1 microglia/macrophage marker Ccl17, while enhancing the expression of the M2 microglia/macrophage marker Arginase 1. Collectively, our findings demonstrate that IL-18 inhibition promotes motor recovery and facilitates the polarization of M1 microglia/macrophages to the M2 phenotype, thereby fostering a neuroprotective immune microenvironment in mice with SCI.https://www.mdpi.com/2218-273X/15/1/16spinal cord injuryneurongliaIL-18neuroinflammationinflammatory response
spellingShingle Easmin Begum
Md Rashel Mahmod
Md Mahbobur Rahman
Fumiko Fukuma
Takeshi Urano
Yuki Fujita
IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
Biomolecules
spinal cord injury
neuron
glia
IL-18
neuroinflammation
inflammatory response
title IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
title_full IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
title_fullStr IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
title_full_unstemmed IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
title_short IL-18 Blockage Reduces Neuroinflammation and Promotes Functional Recovery in a Mouse Model of Spinal Cord Injury
title_sort il 18 blockage reduces neuroinflammation and promotes functional recovery in a mouse model of spinal cord injury
topic spinal cord injury
neuron
glia
IL-18
neuroinflammation
inflammatory response
url https://www.mdpi.com/2218-273X/15/1/16
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AT mdmahboburrahman il18blockagereducesneuroinflammationandpromotesfunctionalrecoveryinamousemodelofspinalcordinjury
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