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.

Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children and young adults. Although MP sometimes causes self-limiting pneumonia, severe and fulminant cases with hypoxia occur, but their clinical features have rarely been reported. This study aimed to reveal the clinical manifestations, risk factors, and treatment of fulminant MP pneumonia (MPP). Using PubMed and abstracts from the proceedings of several domestic Japanese academic societies, we reviewed the Japanese and English literature for cases of fulminant or severe MPP reported in Japan. All clinical information such as sex, age, underlying diseases, clinical symptoms, clinical course, laboratory and radiological findings, and treatment was collected and analyzed. In total, 52 fulminant MPP cases were reported between September, 1979 and February, 2010. The dominant population of fulminant MPP was young adults without severe underlying diseases. Cough (97.3%), fever (100.0%), and dyspnea (83.3%) with diffuse abnormal findings in radiological examinations were noted. Antibiotics without anti-mycoplasmal activity were used in 32 cases (61.5%) as initial treatment prior to the onset of hypoxia. Anti-mycoplasmal drugs were appropriately used in 41 cases (78.8%) after onset of respiratory failure with steroids (23 cases, 45.1%) and effective. The majority of patients improved within 3-5 3 days after steroid administration. There were only 2 fatal cases. Although this small retrospective study did not reveal the apparent risk factors of fulminant MPP, initial inappropriate use of antibiotics may be a risk factor, and early administration of appropriate anti-mycoplasmal drugs with steroids as a cellular immune suppressor is required.4

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We analyzed the relationship between rifampin MICs and rpoB mutations of 40 clinical isolates of Mycobacterium tuberculosis. A point mutation in either codon 516, 526, or 531 was found in 13 strains requiring MICs of > or = 64 micrograms/ml, while 21 strains requiring MICs of < or = 1 microgram/ml showed no alteration in these codons. However, 3 of these 21 strains contained a point mutation in either codon 515 or 533. Of the other six strains requiring MICs between 2 and 32 micrograms/ml, three contained a point mutation in codon 516 or 526, while no alteration was detected in the other three. Our results indicate that the sequencing analysis of a 69-bp fragment in the rpoB gene is useful in predicting rifampin-resistant phenotypes.