A review of the role of high mobility group box 1 in nasal inflammation: Insights from allergic rhinitis and chronic rhinosinusitis

Abstract

Allergic rhinitis and chronic rhinosinusitis are highly prevalent chronic inflammatory disorders of the nasal mucosa that impair sleep, work productivity and negatively impact quality of life; and represent a considerable medical, social, and economic burden to patients and their families. Both conditions are driven by complex immune mechanisms, including epithelial barrier dysfunction, dysregulated innate and adaptive immune responses, and persistent inflammatory signaling. High mobility group box 1 (HMGB1) protein was identified as a key nuclear protein that, when released extracellularly under conditions of cellular stress or injury, acts as a potent danger-associated molecular pattern (DAMP) or alarmin that amplifies inflammation through interactions with certain receptors. Relevant publications were identified through a targeted search of PubMed and Google Scholar, using the terms HMGB1, allergic rhinitis, chronic rhinosinusitis, and nasal inflammation. This review analyzed available evidence regarding the role of HMGB1 in the pathogenesis of allergic rhinitis and chronic rhinosinusitis, emphasizing its association with disease severity, eosinophilic inflammation, and disruption of epithelial homeostasis. The identified studies found increased expression of HMGB1 in the serum, nasal tissues, and airway secretions of affected individuals, as well as enhanced activation of HMGB1-associated receptor pathways. Furthermore, this review summarizes emerging therapeutic approaches targeting HMGB1, including the use of glycyrrhetinic acid, ethyl pyruvate, and resveratrol, which showed favorable anti-inflammatory effects in experimental models and early clinical settings, without significant adverse reactions. These findings suggest that inhibition of HMGB1 may represent a promising therapeutic option for patients with chronic inflammatory diseases of the upper airways. However, continued experimental and clinical research is necessary to validate these results and advance novel treatment strategies that could reduce the burden associated with these disabling conditions.