Significance of IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB)

Abstract

We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The number of neutrophils in BALF obtained from DPB patients was significantly higher than that of healthy volunteers. Treatment with erythromycin (600 mg/day for 12.9+/-9.5 months (mean +/- s.d.)) significantly reduced the total number of cells and neutrophils in the airway, and significantly improved pulmonary function tests. The levels of IL-1beta and IL-8 were significantly higher in DPB compared with healthy volunteers (P<0.05, P<0.05, respectively). IL-1Ra in patients is considered to have a weak inhibitory activity for IL-1beta, with approximately five-fold concentration of IL-1beta compared with that in healthy volunteers (approx. nine-fold concentration of IL-1beta). Erythromycin therapy significantly reduced these cytokines to levels comparable to those of healthy volunteers, and produced a trend toward reduction in the level of IL-1Ra in BALF. The level of IL-1beta correlated significantly with the concentration of neutrophils in BALF (r=0.72, P<0.01), as well as with the level of IL-1Ra (r=0.688, P<0.05) and IL-8 (r=0.653, P<0.05). A nearly significant or significant correlation was observed between the concentration of neutrophils and levels of IL-1Ra or IL-8 in BALF (r=0.526, P=0.053 or r=0.776, P<0.01, respectively). There was also a significant relationship between FEV(1) and the concentration of neutrophils in BALF (r=0.524, P<0.05). Our results suggest that the relative amounts of IL-1beta and IL-1Ra or IL-8 may contribute, at least in part, to the neutrophil-mediated chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cycle between the cytokine network and neutrophil accumulation, with resultant reduction of neutrophil-mediated inflammatory response.

Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia

“…IL-1β was the only significantly decreased pro-inflammatory cytokine in BALF after 12 weeks of azithromycin treatment of patients with COPD [31]. Erythromycin treatment reduced IL-1β in BALF of DPB patients to levels comparable to those of healthy controls [32,33].…”

Epigallocatechin-3-gallate inhibits interleukin-1β-induced MUC5AC gene expression and MUC5AC secretion in normal human nasal epithelial cells

“…The proinflammatory cytokine IL-1β is one of the principal mediators of inflammation and participates in airway diseases characterized by increased mucus production [3,6,18]. The mechanisms that lead to IL-1β-dependent signal transduction are also important in various inflammatory reactions and generally correlate with increased NF-κB activity [19][20][21][22].…”

Accumulation of CXCR3-Expressing Eosinophils and Increased Concentration of Its Ligands (IP10 and Mig) in Bronchoalveolar Lavage Fluid of Patients with Chronic Eosinophilic Pneumonia

“…Concentrations below the detection limits were assumed to be zero for the purposes of statistical analysis. In this study, the absolute concentrations of the cytokines in the BALF rather than values relative to the proteins are reported, since BALF cytokine levels are not influenced by the concentration of albumin, as demonstrated in our previous study [21]. …”

“…After having obtained written informed consent from the subject, bronchoalveolar lavage was performed using a flexible fiberoptic bronchoscope under local anesthesia of the upper airway with 2% lidocaine, as previously described [21]. Briefly, the bronchoscope was wedged into the subsegmental bronchus of the right middle lobe or, in patients with eosinophilic pneumonia, into areas of the lung parenchyma that appeared otherwise normal on the chest roentgenogram.…”