Recently, "low-dose and long-term"
erythromycin (EM) has been reported to be effective in treatment of
diffuse panbronchiolitis (DPB), but its mechanism is still obscure. We studied the effect of EM on
cytokine mRNA expression by using LPS-stimulated human whole blood as an experimental vivo model.
IL-8 mRNA was expressed in biphasic fashion with peak expression at 6 hours and 20 hours from the start of LPS stimulation. When whole blood was pretreated with EM (2 micrograms/ml) for 1 hours.
IL-8 mRNA expression was depressed at 20 hours (p < 0.025) from the start of LPS (1 microgram/ml) stimulation. However, when pretreated for 12 hours, it was not depressed. EM (2 micrograms/ml) also depressed
IL-1 beta (p < 0.025) and
TNF alpha (p < 0.05)
mRNA expressions at 6 hours from the start of LPS stimulation. From the above results, it was suggested that the direct inhibition of
IL-1 beta and
TNF alpha production by EM resulted in subsequent depression of production of
IL-8 that is a potent
chemotactic factor for neutrophil, and consequently, EM acts to protect the bronchiole tissues of DPB patients from destruction by
proteolytic enzymes released from neutrophils. This assumption seems to be supported by our previous observation that when patients with DPB were treated with EM a marked decrease in number of neutrophil in bronchoalveolar lavage fluid (BALF) was accompanied by clinical and radiographic improvement.