Association of serum high-mobility group box protein 1 level with outcomes of acute exacerbation of idiopathic pulmonary fibrosis and fibrosing nonspecific interstitial pneumonia

Background and objective High-mobility group box 1 (HMGB1) protein is important in acute lung injury. However, the role of HMGB-1 in acute exacerbation of fibrosing interstitial pneumonia (AE-FIP) has not been adequately studied. Methods We prospectively measured serum HMGB1 level from disease onset to day 7 in 36 patients with AE-FIP6 patients had missing data because of early death (within 7 days). We then examined the association of HMGB1 level and outcome, and the associations of rhTM with HMGB1 level and outcome in 19 patients who were treated with rhTM (rhTM group) and 11 patients who were not (control group). Results Data from 36 AE-FIP patients (mean age, 73.5 +/- 6.7years) were analyzed. Serum HMGB1 level was significantly higher in patients with AE-FIP than in those with stable idiopathic pulmonary fibrosis (16.4 +/- 13.5 vs 5.7 +/- 2.6 ng/ml, respectively; p = 0.003). HMGB1 was significantly lower on day 7 than at AE-FIP onset in survivors (6.5 +/- 4.8 vs 14.7 +/- 12.9 ng/ml, respectively; p = 0.02) but not in nonsurvivors (14.6 +/- 10.5 vs 9.2 +/- 4.8 ng/ml, respectively; p = 0.08). Although HMGB1 level at day 7 was significantly lower after rhTM treatment than at AE-FIP onset (8.4 +/- 6.1 vs 15.2 +/- 12.5 ng/ml, respectively; p = 0.02), it did not significantly decrease in patients receiving treatments other than rhTM (11.3 +/- 11.3 vs 8.3 +/- 5.3 ng/ml, respectively; p = 0.37). Three-month survival was 60.0% in the rhTM group and 36.4% in the control group (p = 0.449). In multivariate analysis, a decrease in HMGB1 was a significant independent predictor of 3-month survival (Odds ratio, 12.4; p = 0.007). Conclusion rhTM lowers serum HMGB1 level and may improve survival after AE-FIP. HMGB1 may be a promising therapeutic target for AE-FIP.