Recently, "low-dose and long-term" erythromycin treatment has been reported as effective on diffuse panbronchiolitis (DPB), but its mechanism is still obscure. Patients with DPB were found to have significantly higher percentages of neutrophils in the pre-erythromycin treatment bronchoalveolar lavage fluid (BALF) than healthy nonsmoking volunteers (p < 0.001). They showed a significant reduction in BALF neutrophil percentages after erythromycin treatment (p < 0.01). The neutrophil chemotactic activity (NCA) was significantly elevated in BALF obtained from 19 patients with DPB compared with that from healthy volunteers (p < 0.001). A significant reduction in the NCA was observed in post-erythromycin treatment BALF of 11 patients with DPB (p < 0.001). Additionally, there was a significant correlation between the reduction of NCA and neutrophil percentage in pre- and post-erythromycin treatment BALF (r = 0.726, p < 0.05). Finally, we investigated the effect of erythromycin on the intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS) and interleukin-8 (IL-8) in mice. The intrapulmonary influx of neutrophils was significantly suppressed (p < 0.001) in mice intraperitoneally injected with erythromycin at 5 mg per animal 2 h before intratracheal injection of LPS (control group: 6.5 +/- 1.6 x 10(5) versus erythromycin-treated group: 1.7 +/- 0.5 x 10(5)), but not 10 h before lung challenge. This inhibition was observed at 6 h after lung challenge and became maximal with 84% suppression at 24 h. Week-long administration of erythromycin did not alter the intrapulmonary influx of neutrophils. The number of neutrophils in the peripheral blood was not affected by erythromycin, indicating that the drug was not toxic.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the levels of interleukin (IL) 1β, tumor necrosis factor alpha, and IL-8 in bronchoalveolar lavage fluid (BALF) and sera of patients with diffuse panbronchiolitis (DPB) before and after administration of erythromycin or roxithromycin. The pretreatment levels of IL-1β and IL-8 were significantly higher in the BALF of patients with DPB than in the BALF of patients with sarcoidosis and controls. The tumor necrosis factor alpha level was also higher than in controls, but not statistically significant. There was a significant correlation between percentage of neutrophils and IL-8 level in the BALF of DPB patients (r = 0.509; p < 0.05) on the one hand and between IL-1β and IL-8 on the other (r = 0.476; p < 0.04). Treatment for 1-24 months significantly reduced BALF levels of IL-1β and IL-8 of DPB patients in parallel with a reduction in BALF neutrophils. The serum level of IL-8 of DPB patients was higher, albeit insignificant, than that of controls and significantly lower than that in the BALF of the same patients (p = 0.0088). Serum IL-1β was below the detection limit. In addition, the concentration of IL-8 in alveolar macrophages obtained from 2 volunteers before and after oral erythromycin administration also decreased ex vivo. Our results indicate that IL-8 induces the migration of neutrophils to inflammatory sites. It is possible that the macrolides impair production and/or secretion of these cytokines, ultimately reducing neutrophil accumulation in the airway.

IL-ƒÀ p<0.05). These cytokines showed a decrease after RXM treatment. These results indicated that RXM acts by reducing pulmonary inflammation through reduction of neutrophil migration to inflammatory sites, and is effective on chronic lower respiratory tract disease.

Wereport a case of pulmonary infiltration with eosinophilia (PIE), associated with increased serum levels of squamous cell carcinoma-related antigen (SCC) and neuron specific enolase (NSE). The diagnosis of PIE was confirmed by examination ofbronchoalveolar lavage fluid and specimens of transbronchial lung biopsy. It was suggested that PIE was probably induced by a course of amoxicillin for a sore throat. Corticosteroid therapy resulted in clinical improvement of symptoms, resolution of pulmonary infiltrates on chest roentgenogram and reduction in serum levels of SCC andNSE. (Internal Medicine 33: 550-553, 1994)

The mechanisms of erythromycin (EM) in chronic lower respiratory tract diseases including diffuse panbronchiolitis (DPB) has been reported. In this study we investigated the effect of EM on peripheral neutrophil adhesion molecules such as LFA-1 and Mac-1 obtained from six healthy subjects. Pretreatment of neutrophils with each concentration (10 ng/ml approximately 100 micrograms/ml) of EM resulted in no significant reduction in the expression of LFA-1 alpha, beta and Mac-1. Moreover, EM had no capability of reducing these expressions even when neutrophils were pretreated with 1 microgram/ml of EM at time from 0 to 60 min. These findings indicate that EM does not directly reduce the expression of LFA-1 alpha, beta and Mac-1 on peripheral neutrophil obtained from healthy subjects.