IL-33 promotes sciatic nerve regeneration in mice by modulating macrophage polarization

• Published in: International immunopharmacology Vol. 123; p. 110711
• Main Authors: Wasman Smail, Shukur, Ziyad Abdulqadir, Shang, Omar Khudhur, Zhikal, Elia Ishaq, Sonia, Faqiyazdin Ahmed, Abdullah, Ghayour, Mohammad B., Abdolmaleki, Arash
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2023
• Subjects: Cytokine; IL-33; Inflammation; Macrophage; Sciatic Nerve; PWRL; DMSO; BDNF; VEGF; CMAP; Cytokine; CNS; Inflammation; PNI; MAPK; NGF; IL-33; ECM; NF-κB; IL-1RAP; SFI; SCI; Sciatic Nerve; Macrophage
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110711

•IL-33 treatment as a chemokine recruits macrophages and potentiates type 2 immune response.•IL-33 administration could significantly accelerate regeneration and improve sensorimotor recovery by polarized macrophages toward the M2 phenotype and attenuated the pro-inflammatory response in the injured nerve.
Despite the innate regenerative capacity of peripheral nerves, regeneration after a severe injury is insufficient, and sensorimotor recovery is incomplete. As a result, finding alternative methods for improving regeneration and sensorimotor recovery is essential. In this regard, we investigated the effect of IL-33 treatment as a chemokine with neuroprotective properties. IL-33 can facilitate tissue healing by potentiating the type 2 immune response and polarizing macrophages toward the pro-healing M2 phenotype. However, its effects on nerve regeneration remain unclear. Therefore, this research aimed to evaluate the neuroprotective effects of IL-33 on sciatic nerve injury in male C57BL/6 mice. After crushing the left sciatic nerve, the animals were given 10, 25, or 50 µg/kg IL-33 intraperitoneally for seven days. The sensorimotor recovery was then assessed eight weeks after surgery. In addition, immunohistochemistry, ELISA, and real-time PCR were used to assess macrophage polarization, cytokine secretion, and neurotrophic factor expression in the injured nerves. IL-33 at 50 and 25 µg/kg doses could significantly accelerate nerve regeneration and improve sensorimotor recovery when compared to 10 µg/kg IL-33 and control groups. Furthermore, at 50 and 25 µg/kg doses, IL-33 polarized macrophages toward an M2 phenotype and reduced proinflammatory cytokines at the injury site. It also increased the mRNA expression of NGF, VEGF, and BDNF. These findings suggest that a seven-day IL-33 treatment had neuroprotective effects in a mouse sciatic nerve crush model, most likely by inducing macrophage polarization toward M2 and regulating inflammatory microenvironments.