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

Overview

Journal Biomolecules

Publisher MDPI

Date 2025 Jan 25

PMID 39858411

Authors

Easmin Begum

Md Rashel Mahmod

Md Mahbobur Rahman

Fumiko Fukuma

Takeshi Urano

Yuki Fujita

Affiliations

Soon will be listed here.

Abstract

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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