SIGNIFICANCE OF IL-1-BETA AND IL-1 RECEPTOR ANTAGONIST (IL-1RA) IN BRONCHOALVEOLAR LAVAGE FLUID (BALF) IN PATIENTS WITH DIFFUSE PANBRONCHIOLITIS (DPB)

We evaluated the effect of erythromycin therapy on pulmonary function tests and the airway inflammatory response of patients with DPB. The n umber of neutrophils in BALF obtained from DPB patients was significan tly higher than that of healthy volunteers. Treatment with erythromyci n (600 mg/day for 12.9 +/- 9.5 months (mean +/- s.d.)) significantly r educed the total number of cells and neutrophils in the airway, and si gnificantly improved pulmonary function tests. The levels of IL-1 beta and IL-8 were significantly higher in DPB compared with healthy volun teers (P < 0.05, P < 0.05, respectively). IL-1Ra in patients is consid ered to have a weak inhibitory activity for IL-1 beta, with approximat ely five-fold concentration of IL-1 beta compared with that in healthy volunteers (approx. nine-fold concentration of IL-1 beta). Erythromyc in 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-1 beta correlated sign ificantly 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 correl ation 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 < 0.0 1, respectively). There was also a significant relationship between FE V(1) and the concentration of neutrophils in BALF (r = 0.524, P < 0.05 ). Our results suggest that the relative amounts of IL-1 beta and IL-1 Ra or IL-8 may contribute, at least in part, to the neutrophil-mediate d chronic airway inflammation in patients with chronic airway disease, and long-term erythromycin therapy may down-regulate the vigorous cyc le between the cytokine network and neutrophil accumulation, with resu ltant reduction of neutrophil-mediated inflammatory response.