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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2024-12-01
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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. |
| format | Article |
| id | doaj-art-4ff88048e92e4162b0cde69c0f2f4b58 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
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| series | Biomolecules |
| 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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