Effects of Roxithromycin on Proliferation of Peripheral Blood Mononuclear Cells and Production of Lipopolysaccharide-Induced Cytokines.

Yoshimura, Tomoaki; Kurita, Chikako; Yamazaki, Futoshi; Shindo, Jo; Morishima, Itsuro; Machida, Kazuya; Sumita, Tatsuya; Horiba, Michiaki; Nagai, Hiroichi

doi:10.1248/bpb.18.876

Cited by 26 publications

(10 citation statements)

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“…It has been shown in in vitro studies that macrolides modulate the proliferation, differentiation, cytokine production and phagocytosis of monocytes, macrophages and lymphocytes [25][26][27][28][29][30][31]. Macrolides also improve the ciliary movement of airway epithelial cells [32], inhibit bacterial adherence to ciliated epithelial cells [33], suppress IL-8 production from airway epithelial cells and exudative neutrophils [34][35][36] and inhibit glycoprotein and electrolyte secretion from airway epithelial cells and nasal gland cells [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Chronic Rhinosinusitis under Long-Term Low-Dose Macrolide Therapy

Suzuki

Ikeda

Honma

et al. 2000

ORL

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We studied the immunological and histopathological factors that affect the prognosis of chronic rhinosinusitis under long-term low-dose macrolide therapy. Sixteen patients with chronic rhinosinusitis were given 200 mg clarithromycin or 150 mg roxithromycin orally once a day without other concurrent treatments for 2–3 months. Measurement of the serum IgE level, blood cell count and differential leukocyte count of the peripheral blood, cytological assessment of the nasal smear and computed tomographic (CT) scans of the paranasal sinuses were performed before treatment. The opacity of the sinuses was estimated and scored by the CT images. After treatment, anterior ethmoidal mucosa samples were collected, an infiltrated inflammatory cells, interferon (IFN)-γ-positive cells and interleukin (IL)-4-positive cells were examined histologically and immunohistochemically. The severity of nasal symptoms was scored before and after treatment, and the improvement rate of the score (symptomatic improvement rate) was calculated. Patients with normal levels of serum IgE (≤250 U/ml) showed a significantly higher symptomatic improvement rate than those with high levels of serum IgE (42.1 ± 11.2 vs. 4.9 ± 3.1%, p = 0.046). The symptomatic improvement rate was inversely correlated with the eosinophil counts in the peripheral blood (r = –0.51, p = 0.04), in the nasal smear (r = –0.54, p = 0.045) and in the sinus mucosa (r = –0.54, p = 0.02). Meanwhile, the CT score, the number of IFN-γ-positive cells and IL-4-positive cells in the sinus mucosa and neutrophil counts in the nasal smear and in the sinus mucosa failed to correlate with the symptomatic improvement rate. These results suggest that macrolide therapy is indicated for patients without atopy or smear/tissue/peripheral blood eosinophilia. On the contrary, the severity of the disease, Th1/Th2 dominance in the sinus mucosa and neutrophilia are unlikely to be prognostic factors of chronic rhinosinusitis under long-term low-dose marolide therapy.

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Section: Discussionmentioning

confidence: 99%

Prognostic Factors of Chronic Rhinosinusitis under Long-Term Low-Dose Macrolide Therapy

Suzuki

Ikeda

Honma

et al. 2000

ORL

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“…Roxithromycin, for example, inhibits the production of interleukin (IL)-1b and tumor necrosis factor (TNF)-a in human peripheral blood monocytes in a dose-dependent manner [5]. Roxithromycin also has an inhibitory effect on IL-8 and on intercellular adhesion molecule (ICAM)-1 expression in human bronchial epithelial cells [6].…”

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confidence: 99%

Effect of Macrolide Antibiotics on Human Endothelial Cells Activated byChlamydia pneumoniaeInfection and Tumor Necrosis Factor–α

et al. 2002

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This study investigated the potential anti-inflammatory activity of 3 macrolide antibiotics, clarithromycin, roxithromycin, and azithromycin, in an in vitro model of transendothelial migration (TEM). Human umbilical vein endothelial cells (HUVECs) were seeded in Transwell inserts, treated with serial dilutions of the antibiotics, and infected with Chlamydia pneumoniae or stimulated with tumor necrosis factor (TNF)-alpha. In HUVECs infected with C. pneumoniae or stimulated with TNF-alpha, both azithromycin and roxithromycin caused significant decreases in neutrophil and monocyte TEM, compared with antibiotic-free controls. Clarithromycin had no detectable effect in either group. Azithromycin caused significant decreases in interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, whereas roxithromycin significantly decreased IL-8. This study indicates heterogeneity in the anti-inflammatory activity of these antibiotics. Mechanisms of monocyte and neutrophil TEM inhibition by azithromycin and roxithromycin are unclear but may be partially due to inhibition of IL-8 and MCP-1 production.

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“…We did not find any reports about the genotoxic potential of RXM, although in our unpublished study, RXM did not show any genotoxic effect in human lymphocytes in chromosome aberration, sister chromatid exchange, and micronucleus tests. When we talk about cytotoxicity of RXM, there are some studies showing the anti-proliferative effect of RXM (Dai et al, 2014;Yatsunami et al, 1999;Yoshimura et al, 1995). On the contrary, one study reported that RXM had anti-cytotoxic effect against sulfur mustard in human respiratory epithelial cells (Gao et al', 2007).…”

Section: Introductionmentioning

confidence: 99%

In vitrocytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin

Timocin

Hüsunet

Valipour

et al. 2016

Drug and Chemical Toxicology

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Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 μg/mL + 25 μg/mL, 15 μg/mL + 50 μg/mL, and 20 μg/mL + 100 μg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively. The effect of the combination in aspect of anti-oxidative and DNA damaging activity was evaluated on Pet-22b plasmid. According to our results, the combination of FLB and RXM did not show a notable genotoxic effect on cells. Although each of the substances had been shown as a cytotoxic agent by previous researchers, in this research, the combination of these drugs did not exhibit any adverse effect on cell division. FLB had DNA protection effect against HO while in combination with RXM had not the same effect on the plasmid.

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Effects of Roxithromycin on Proliferation of Peripheral Blood Mononuclear Cells and Production of Lipopolysaccharide-Induced Cytokines.

Cited by 26 publications

References 0 publications

Prognostic Factors of Chronic Rhinosinusitis under Long-Term Low-Dose Macrolide Therapy

Prognostic Factors of Chronic Rhinosinusitis under Long-Term Low-Dose Macrolide Therapy

Effect of Macrolide Antibiotics on Human Endothelial Cells Activated byChlamydia pneumoniaeInfection and Tumor Necrosis Factor–α

In vitrocytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin

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