[Mechanism of efficacy of erythromycin on diffuse panbronchiolitis--effect of erythromycin on cytokine mRNA expression in human whole blood model].
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.
Akiyoshi
H
H
First Department of Medicine, Kurume University.
Honda
J
J
Nakahara
S
S
Tokisawa
S
S
Tokunaga
N
N
Ichikawa
Y
Y
Oizumi
K
K
D000328:Adult; D001483:Base Sequence; D001988:Bronchiolitis / Q000188:drug therapy*; D016207:Cytokines / Q000235:genetics*; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin