Active immunotherapy against IL-1β restores tissue repair under chronic inflammation

Chronic inflammation driven by sustained interleukin-1 beta (IL-1β) signaling disrupts the resolution phase of tissue repair by orchestrating dysregulated immune activity. As a key upstream mediator, IL-1β prolongs the activation of pro-inflammatory myeloid cells and establishes an environment that prevents the transition to tissue repair. Here, we developed an active immunotherapy against IL-1β using the self-assembling peptide nanofiber Coil29, which elicits robust and specific IL-1β-targeted immune responses in both wild-type and diabetic mice, without inducing systemic immunosuppression. In a chronic wound model, the therapy accelerated re-epithelialization and enhanced overall tissue regeneration, outperforming anti-IL-1β monoclonal antibodies. This therapy suppressed macrophage activity, promoted their M2-like polarization, enhanced pro-healing cytokine secretion and enriched the injury site with anti-IL-1β antibodies. In vitro, we found that antibodies from immunized mice reprogrammed M1 macrophages toward an M2-like phenotype, suggesting that antibody-mediated modulation of IL-1β activity may drive the enhanced wound re-epithelization seen in immunized animals. Altogether, these findings highlight a targeted, regenerative therapy for the healing of chronic wounds.