Increased levels of HMGB-1 and endogenous secretory RAGE in induced sputum from asthmatic patients

Abstract

Background: High mobility group box 1 (HMGB-1), a ligand of the receptor for advanced glycation end products (RAGE), is an inflammatory mediator in various disorders. Its endogenous decoy inhibitor, endogenous secretory RAGE (esRAGE), prevents the activation of RAGE signaling, and imbalance between HMGB-1 and esRAGE is known to be a factor determining progression of chronic inflammatory diseases.

Methods: We measured HMGB-1 and esRAGE levels in induced sputum from 44 asthmatic patients and 15 normal controls, and examined their correlations with asthma indices including pulmonary function test values and induced sputum indices.

Results: HMGB-1 levels in induced sputum were significantly higher in asthmatic patients than in normal controls (p < 0.001). Similarly, esRAGE levels were significantly higher in asthmatic patients than in normal controls (p < 0.001). In asthmatic patients, HMGB-1 levels were inversely correlated with percentage of predicted forced expiratory volume in 1 s (%FEV(1)) and FEV(1)/forced vital capacity (FEV(1)/FVC). There was a significant increase in HMGB-1 level associated with severity of asthma (p < 0.001). However, there was no significant increase in esRAGE level associated with severity of asthma. In asthmatic patients, HMGB-1 levels were significantly correlated with percentage of neutrophils in induced sputum.

Conclusions: Our findings suggest that the HMGB-1 is a mediator of neutrophilic airway inflammation in asthma and that imbalance between HMGB-1 and esRAGE is related to the severity of asthma. Combined measurement of HMGB-1 and esRAGE may be novel biomarkers in asthma with severe airflow limitation.