Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases

Oishi, Kazunori; Sonoda, Fuminari; Kobayashi, Shinobu; Iwagaki, Akitaka; Nagatake, Tsuyoshi; Matsushima, Kouji; Matsumoto, Keizō

doi:10.1128/iai.62.10.4145-4152.1994

Cited by 186 publications

(80 citation statements)

References 50 publications

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“…36,72 The level of IL-8 in BAL fluid markedly decreases along with the neutrophil number and its elastase concentration. 73 EM dose-dependently inhibited IL-8, IL-6 and granulocyte-macrophage colony-stimulating factor secretion from epithelial cells in vitro using a human airway epithelial cell line. 74,75 Recently, it was revealed that EM suppressed the activation of nuclear factor-kappa B and activator protein-1 in human bronchial epithelial cells and subsequently inhibited IL-8 mRNA expression on epithelial cells.…”

Section: Inhibition Of Neutrophil Activitymentioning

confidence: 93%

Diffuse panbronchiolitis in East Asia

Azuma

Kudoh

2006

Respirology

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Diffuse panbronchiolitis in East AsiaAZUMA A, KUDOH S. Respirology 2006; 11: 249-261 Abstract: Diffuse panbronchiolitis is characterized by chronic sinobronchial infection and diffuse bilateral centrilobular lesions consisting of peribronchial infiltration of inflammatory cells. At present, it is known that diffuse panbronchiolitis is relatively restricted to East Asia. This uneven distribution is suspected to be highly associated with genetic predisposition located between human leucocyte antigen-A and -B loci. Low-dose, long-term macrolide therapy for the disease was suggested from a detailed observation of a single case that significantly improved by erythromycin therapy. Otherwise simple bactericidal activity of macrolides has been assumed as a candidate because of their clinical effect on the pathogenesis. In the last 10 years, the possible mechanism underlying the effectiveness of macrolide therapy has been dynamically investigated. To understand the pathological features and potential targets for macrolides in diffuse panbronchiolitis, the authors introduce the incidence of diffuse panbronchiolitis in East Asia, the profile of the disease and then trace the history of macrolide therapy in this review. The proposed mechanism of action includes the inhibition of excessive mucus and water secretion from the airway, the inhibition of neutrophil, and sometimes of lymphocyte and macrophage accumulating in the airway, the inhibition of transcription factors expressing several cytokines and the attenuation of bacterial virulence. Intracellular mechanisms of the action of macrolide are a hot topic of interest in research. The anti-inflammatory activity of macrolides is independent of their bactericidal effect, and a new anti-inflammatory analogue without antimicrobial activity should be developed to minimize the emergence of macrolideresistant microorganisms and to maintain the safety of this treatment.

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Section: Inhibition Of Neutrophil Activitymentioning

confidence: 93%

Diffuse panbronchiolitis in East Asia

Azuma

Kudoh

2006

Respirology

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“…Earlier studies found that macrolide antibiotics influence the endotoxin-induced production of cytokines by the host, as well as production induced by Gram positive bacteria [13][14][15][16][17]. However, the clinical relevance of this finding is uncertain.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic‐pharmacodynamic modeling of the inhibitory effect of erythromycin on tumour necrosis factor‐α and interleukin‐6 production

Guchelaar

Schultz

Poll

et al. 2001

Fundamemntal Clinical Pharma

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Erythromycin inhibits the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) induced by heat-killed Streptococcus pneumoniae in human whole blood ex-vivo. The objective of the present study was to determine and characterize the concentration-effect relationship of this phenomenon in order to predict its possible clinical relevance. Six healthy volunteers received a single intravenous dose of 1000 mg erythromycin. Blood samples were obtained up to 4 h after drug administration. Samples were assayed for erythromycin concentrations and (after heat-killed Streptococcus pneumoniae stimulation) for TNF-alpha and IL6 concentrations. Effect vs. time data from individual subjects were fitted to the indirect response model with an Emax concentration-effect relationship. Simulations of these effects were performed for therapeutic intravenous and oral erythromycin dosage regimens. The geometric means of the values of Kin, Kout and EC50 were 15.4 microg/h, 0.82/h, 9.4 mg/L for TNF-alpha and 321 microg/h, 2.02/h, 18.3 mg/L for IL6. Simulations revealed a maximal inhibition of TNF-alpha concentrations of 35%, 50%, 16% and 27% at erythromycin dosages of 500 mg i.v., 1000 mg i.v., 500 mg p.o and 1000 mg p.o. q 6 h, respectively, whereas a maximal inhibition of IL6 of 29%, 44%, 13% and 22% are predicted for the respective regimens. The inhibitory effect of erythromycin on TNF-alpha and IL6 production can be adequately described by the indirect response model with an Emax concentration-effect relationship. Simulations predicted a substantial decrease of production of these cytokines at intravenous and to a much lesser extent at oral erythromycin dosage regimens.

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“…We tried long-term low-dose erythromycin therapy in the present patient because of its anti-inflammatory effects. 13,14 Low-dose erythromycin therapy led to disappearance of recurrent pneumonia. However, we could not sufficiently explain the mechanism of efficacy of low-dose erythromycin therapy in recurrent pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Elderly patient with short‐term recurrent pneumonia in the same lobe

Yamanari

Tada

2003

Geriatrics Gerontology Int

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After complaints of fever, cough and a right upper lateral chest pain, an 86‐year‐old man received medical examination in January 2001. A chest X‐ray showed right upper pulmonary infiltrates. He was empirically treated and the pulmonary infiltrates disappeared. He had a second episode of recurrent pneumonia in the same right upper lobe in April 2001, and then a third episode of recurrent pneumonia in October 2001. Chest computed tomography showed neither localized intraluminal bronchial obstruction nor localized extrinsic bronchial compression in the right upper pulmonary lobe. His immune system and pulmonary function tests were normal. Therefore, it appeared that these were the same lobar recurrent pneumonias, which are rare in the short term. He was tried on long‐term low‐dose erythromycin therapy after the third episode of recurrent pneumonia and he has had no recurrent pneumonia for 16 months.

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Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases

Cited by 186 publications

References 50 publications

Diffuse panbronchiolitis in East Asia

Diffuse panbronchiolitis in East Asia

Pharmacokinetic‐pharmacodynamic modeling of the inhibitory effect of erythromycin on tumour necrosis factor‐α and interleukin‐6 production

Elderly patient with short‐term recurrent pneumonia in the same lobe

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