INTERLEUKIN-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, AND INTERLEUKIN-8 INBRONCHOALVEOLAR LAVAGE FLUID OF PATIENTS WITH DIFFUSE PANBRONCHIOLITIS - A POTENTIAL MECHANISM OF MACROLIDE THERAPY

We measured the levels of interleukin (IL) 1 beta, tumor necrosis fact or alpha, and IL-8 in bronchoalveolar lavage fluid (BALF) and sera of patients with diffuse panbronchiolitis (DPB) before and after administ ration of erythromycin or roxithromycin. The pretreatment levels of IL -1 beta and IL-8 were significantly higher in the BALF of patients wit h DPB than in the BALF of patients with sarcoidosis and controls. The tumor necrosis factor alpha level was also higher than in controls, bu t not statistically significant. There was a significant correlation b etween percentage of neutrophils and IL-8 level in the BALF of DPB pat ients (r = 0.509; p < 0.05) on the one hand and between IL-1 beta and IL-8 on the other (r = 0.476; p < 0.04). Treatment for 1-24 months sig nificantly reduced BALF levels of IL-1 beta and IL-8 of DPB patients i n parallel with a reduction in BALF neutrophils. The serum level of IL -8 of DPB patients was higher, albeit insignificant, than that of cont rols and significantly lower than that in the BALF of the same patient s (p = 0.0088). Serum IL-1 beta was below the detection limit. In addi tion, the concentration of IL-8 in alveolar macrophages obtained from 2 volunteers before and after oral erythromycin administration also de creased ex vivo. Our results indicate that IL-8 induces the migration of neutrophils to inflammatory sites. It is possible that the macrolid es impair production and/or secretion of these cytokines, ultimately r educing neutrophil accumulation in the airway.