Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages

Sugiyama, Yukihiko; Yanagisawa, Ken; Tominaga, S; Kitamura, Satoshi

doi:10.1183/09031936.99.14511139

Cited by 33 publications

(20 citation statements)

References 18 publications

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“…Because muscular edema has been shown as a result of microvascular permeability induced by vascular endothelial cell damage due to free radicals (14), vascular endothelial cells (ECs) would possibly be a critical determinant of free radical-induced tissue injury. This also suggests that MCI-186 may target ECs in the model used in the present study, and this is supported by the current results indicating the suppression of ICAM-1 expression that is specifically induced by ECs and, inversely, the lack of any effect on the expression of GRO/CINC-1 that is expressed by other cell types, including monocyte/macrophages (27). This is well supported by an in vitro experiment indicating the preventive effect of MCI-186 on vascular EC injury (35), so it is reasonable to conclude that vascular EC injury due to free radicals is the major cause of MNMS and that MCI-186 protects ECs from radical species.…”

Section: Discussionsupporting

confidence: 76%

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

Kaneko

Yonemitsu

Fujii

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia. Am J Physiol Heart Circ Physiol 290: H1484 -H1492, 2006. First published November 23, 2005 doi:10.1152/ajpheart.01006.2005The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed. fibroblast growth factor-2; free radicals; critical limb ischemia; neutrophils IN THE LAST DECADE, a number of experimental studies have suggested the possible utility of angiogenic growth factors ("therapeutic angiogenesis") to treat limb ischemia, as well as ischemic heart diseases (30,31,36). Emerging evidence in clinical trials for limb ischemia, however, has shown a relatively limited outcome of therapeutic angiogenesis, in both protein and gene therapies, in double-blinded placebo-controlled studies (17,23,26). Therefore, further effort should be put into the clinical evaluation of the potentials of therapeutic angiogenesis, including the choice of the angiogenic factors, optimized dose and local level of the dose, and indications for clinical stages (4, 5).In a recent series of experimental studies, we demonstrated that intramuscularly boosted expression of basic fibroblast growth factor (bFGF or FGF-2), which is a prototype polypeptide for angiogenesis, by a highly efficient gene transfer vector, recombinant Sendai virus (SeV) (37), constantly showed efficient therapeutic effects in acute severe hindlimb ischemia of mice (19,21,25,32), as well as chronic limb ischemia of rabbits (2...

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Section: Discussionsupporting

confidence: 76%

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

Kaneko

Yonemitsu

Fujii

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Macrolide antibiotics modulate inflammation in vitro and in vivo by inhibiting the production of proinflammatory cytokines and prostaglandin E 2 , neutrophil chemotactic activity, and elastase activities (14,25,27,28,34,35,38,40,41). Clarithromycin inhibits the production of IL-1, IL-6, IL-8, and TNF-␣ (25,28).…”

Section: Discussionmentioning

confidence: 99%

“…We examined whether or not clarithromycin inhibits the activation of NF-B induced by tumor necrosis factor alpha (TNF- Proinflammatory cytokines are important mediators in inflammation. Macrolide antibiotics exert anti-inflammatory effects through inhibition of the production of proinflammatory cytokines (25,28,35,38,40,41). Clarithromycin is a 14-member lactone ring macrolide antibiotic which has been used for the treatment of infectious diseases.…”

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confidence: 99%

Clarithromycin Inhibits NF-κB Activation in Human Peripheral Blood Mononuclear Cells and Pulmonary Epithelial Cells

Ichiyama

Nishikawa

Yoshitomi

et al. 2001

Antimicrob Agents Chemother

122

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Macrolide antibiotics modulate the production of proinflammatory cytokines in vivo and in vitro. Transcription of the genes for these proinflammatory cytokines is regulated by nuclear factor B (NF-B). We examined whether or not clarithromycin inhibits the activation of NF-B induced by tumor necrosis factor alpha (TNF- Proinflammatory cytokines are important mediators in inflammation. Macrolide antibiotics exert anti-inflammatory effects through inhibition of the production of proinflammatory cytokines (25,28,35,38,40,41). Clarithromycin is a 14-member lactone ring macrolide antibiotic which has been used for the treatment of infectious diseases. It is unclear how clarithromycin suppresses the production of proinflammatory cytokines, but it is not unreasonable to suspect that it inhibits the transcription of multiple cytokine genes.␣Nuclear factor B (NF-B) is a ubiquitous and important transcription factor for genes that encode proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor alpha (TNF-␣) (7,12,17,19,26). The prototype of NF-B is a heterodimer consisting of p50 and p65 bound by members of the IB family, including IB␣, in the cytoplasm (2, 3). NF-B activation requires degradation of the IB protein (10, 11). Phosphorylation of IB␣ by drugs, cytokines, bacterial products, and viruses rapidly leads to IB degradation and translocation of NF-B to the nucleus (5, 16). Activation of NF-B results in the binding of specific promoter elements and expression of mRNAs for proinflammatory cytokine genes (7,12,17,19,26). We tested the hypothesis that clarithromycin modulates inflammation by inhibiting NF-B activation in experiments on human monocytic U-937 cells, a T-cell line (Jurkat), a pulmonary epithelial cell line (A549), and peripheral blood mononuclear cells (PBMC) stimulated by TNF-␣ or staphylococcal enterotoxin A (SEA). MATERIALS AND METHODSCell culture, isolation, and stimulation conditions. A549 cells were obtained from the American Type Culture Collection and maintained at 37°C under humidified 5% CO 2 as a stationary culture. The cells were grown in Dulbecco's modified Eagle's medium containing 4.5 g of glucose/liter and supplemented with 10% fetal bovine serum (FBS), 10 mM L-glutamine, and 100 U of penicillin and 100 g of streptomycin/ml. The day before each experiment, cells were seeded into six-well tissue culture dishes (Costar, Cambridge, Mass.) at the density of 10 6 cells/well.U-937 cells, a human monocytic leukemia cell line, and Jurkat cells, a human T-cell leukemia line, were maintained at 37°C under humidified 5% CO 2 as stationary cultures. Both types of cells were grown in RPMI 1640 medium containing 10% FBS and 100 U of penicillin and 100 g of streptomycin/ml. PBMC were obtained from heparinized blood by Histopaque 1077 (Sigma Chemical Co., St. Louis, Mo.) gradient centrifugation, and the mononuclear cells were resuspended in RPMI 1640 medium containing 10% FBS and 100 U of penicillin and 100 g of streptomycin/ml. Cells were exposed to 100 pM TNF-␣ (R&D S...

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“…The antimicrobial activities of macrolides are generally considered to be produced through the inhibition of microbial protein synthesis by acting on the 50S subunit of the 70S ribosome (36). In addition, macrolide antibiotics exert anti-inflammatory effects by inhibition of the production of proinflammatory cytokines (22,33,35). Moreover, the pharmacokinetics (PK) of macrolides is characterized by a combination of low serum concentrations and high tissue concentrations (40), with advanced-generation macrolides being highly concentrated within polymorphonuclear leukocytes.…”

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confidence: 99%

Efficacy of Clarithromycin against Experimentally Induced Pneumonia Caused by Clarithromycin-Resistant Haemophilus influenzae in Mice

Nakamura¹,

Yanagihara

Araki

et al. 2010

Antimicrob Agents Chemother

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Clarithromycin is a 14-member lactone ring macrolide with potent activity against Haemophilus influenzae, including ampicillin-resistant strains. We evaluated the in vivo efficacy of clarithromycin at 40 mg/day and 100 mg/day for 3 days in the treatment of a murine model of pneumonia using a macrolide-resistant H. influenzae strain, which was also ampicillin resistant. The MIC of clarithromycin was 64 g/ml. The viable bacterial counts in infected tissues after treatment with 100 mg clarithromycin/kg of body weight were lower than the counts obtained in control and 40-mg/kg clarithromycin-treated mice. The concentrations of macrophage inflammatory protein 2 (MIP-2) and interleukin 1␤ (IL-1␤) in bronchoalveolar lavage fluid (BALF) samples from mice treated at both concentrations were lower than in the control group. Pathologically, following infection, clarithromycin-treated mice, particularly at a dose of 100 mg/kg, showed lower numbers of neutrophils in alveolar walls, and inflammatory changes had apparently improved, whereas large aggregates of inflammatory cells were observed within the alveoli of control mice. In addition, we demonstrated that clarithromycin has bacteriological effects against intracellular bacteria at levels below the MIC. Our results indicate that clarithromycin may be useful in vivo for macrolide-resistant H. influenzae, and this phenomenon may be related to the good penetration of clarithromycin into bronchoepithelial cells. We also believe that conventional drug susceptibility tests may not reflect the in vivo effects of clarithromycin.

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Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages

Cited by 33 publications

References 18 publications

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia

Clarithromycin Inhibits NF-κB Activation in Human Peripheral Blood Mononuclear Cells and Pulmonary Epithelial Cells

Efficacy of Clarithromycin against Experimentally Induced Pneumonia Caused by Clarithromycin-Resistant Haemophilus influenzae in Mice

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