title: Increase in the Level of Proinflammatory Cytokine HMGB1 in Nasal Fluids of Patients With Rhinitis and its Sequestration by Glycyrrhizin Induces Eosinophil Cell Death.
abstract: OBJECTIVE
  The nuclear protein high mobility group protein box 1 (HMGB1) is a proinflammatory mediator that belongs to the alarmin family of proinflammatory mediators, and it has recently emerged as a key player in different acute and chronic immune disorders. Several lines of evidence demonstrate that HMGB1 is actively released extracellularly from immune cells or passively released from necrotic cells. Because of the ability of HMGB1 to sustain chronic inflammation, we investigated whether the protein is present in nasal fluids of patients with different forms of rhinitis.
  
  
  METHODS
  HMGB1 levels were evaluated in nasal fluids of healthy subjects or rhinitis patients who were treated or not treated with different treatments.
  
  
  RESULTS
  We report that the level of HMGB1 was significantly increased in nasal fluids of patients with allergic rhinitis, patients with NARES (nonallergic rhinitis with eosinophiliac syndrome), as well as patients with polyps. We also found that a formulation containing the HMGB1-binding compound glycyrrhizin (GLT) reduced the HMGB1 content in nasal fluids of rhinitis patients to an extent similar to that with nasal budesonide treatment. We also found that among the cultured human leukocyte populations, eosinophils released higher amounts of HMGB1. Based on the ability of HMGB1 to sustain eosinophil survival and the ability of GLT to inactivate HMGB1, we report that GLT selectively killed cultured eosinophils and had no effect on neutrophils, macrophages, and lymphocytes.
  
  
  CONCLUSIONS
  Collectively, these data underscore the role of HMGB1 in rhinitis pathogenesis and the therapeutic potential of GLT formulations in treatment of chronic inflammatory disorders of the nasal mucosa.
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Cavone
authors.affiliation: Department of Pediatrics, Unit of Genetic and Immunology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cuppari
authors.affiliation: Department of Pediatrics, Unit of Genetic and Immunology, University of Messina, Messina, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Manti
authors.affiliation: Department of Pediatrics, Unit of Genetic and Immunology, University of Messina, Messina, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Grasso
authors.affiliation: Department of Pediatrics, Unit of Genetic and Immunology, University of Messina, Messina, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Calamai
authors.affiliation: Department of Pediatrics, Unit of Genetic and Immunology, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Firenze, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarugi
keywords: Eosinophils; Glycyrrhizin acid; HMGB1 protein; Rhinitis