Targeting Immune Dysregulation After Burn Injury for Improved Healing and Outcomes.

Burn injury induces profound immune dysregulation that extends beyond the acute phase of wound healing, contributing to complications such as delayed repair, infection, and long-term immune dysfunction. Importantly, these effects are not restricted to severe trauma, as similar immune alterations occur following small- to moderate-sized burns. Despite increasing recognition of post-burn immune dysregulation, targeted immunomodulatory therapies remain limited. In this review, we synthesize current insights into the mechanisms driving immune dysfunction after burn injury and outline therapeutic strategies aimed at restoring immune homeostasis. We examine approaches targeting inflammatory triggers and mediators, including acute clinical interventions, reduction in microbial burden, and inhibition of immune cell activation through systemic and local delivery. We also explore strategies to modulate dysregulated innate immune responses by targeting cell-specific functions, such as neutrophil activity and monocyte/macrophage polarization. Persistent activation and exhaustion of the adaptive immune system may be alleviated through interventions such as β-adrenergic blockade, while metabolic, endocrine, and oxidative stress pathways represent additional therapeutic targets. Finally, we highlight key challenges, including the need for improved diagnostics, early prognostic stratification, and personalized treatment approaches to improve outcomes following burn injury.