Objective: Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms.
Methods: C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot.
Results: IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88.
Conclusions: IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.
Keywords: IL-37; Microglia; MyD88; NF-κB; Neuroinflammation.
© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.