Immunomodulatory Effects of Antimicrobial Drugs

Ruh, Christine; Banjade, Rashmi; Mandadi, Subhadra; Marr, Candace; Sumon, Zarchi; Crane, John K.

doi:10.1080/08820139.2017.1373900

Cited by 10 publications

(7 citation statements)

References 86 publications

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“…Nowadays, the exploration on immunological activity of antimicrobial agents has been exemplified by many successes (Ruh et al, 2017). For example, anti-inflammatory and immunomodulatory properties of macrolide antibiotics have been applied in patients with chronic airways diseases (Ratjen et al, 2012; Wong et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Colistin on Macrophages in Rats by Activating the p38/MAPK Pathway

et al. 2019

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Objectives: Colistin has been identified in a Caenorhabditis elegans chemical screening as an immunostimulatory agent that activates the conserved p38/PMK-1 pathway and provides protection against pathogens. Here we aimed to extend those findings to a mammalian model and evaluate the immunomodulatory effects of colistin on rat macrophages. Methods: Macrophages were isolated from Sprague-Dawley (SD) rat. The effects of colistin on the cytokine secretion, phagocytic activity and protein expression were determined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and Western blotting analysis, respectively. The relative microRNA expression was determined by microarray, and Kyoto Encylopedia of Genes and Genomes (KEGG) was used to identify potential signaling pathways. Results: Our data showed that 5, 10, and 20 µg/ml colistin significantly increased the secretion of TNF-α, while 20 and 5 µg/ml colistin significantly increased the levels of IL-1β and IL-6, respectively. Flow cytometry results showed that the relative mean fluorescence intensity and percentage of phagocytosis in colistin treatment groups were significantly higher compared with the control group, while the increased phagocytosis phenomenon can be blocked by p38 inhibitor. The phagocytic ability of macrophages against Staphylococcus aureus was significantly increased after colistin treatment. Microarray and KEGG pathway analyses revealed that mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), chemokine, and B cell receptor were the main pathways involved in the colistin stimulation process. Western blotting analysis demonstrated that the phosphorylated p38 protein level of colistin treatment groups was increased in a dose dependent manner. Conclusions: Present study is the first to demonstrate that colistin had immunomodulatory effects on macrophages in mammals, and the p38/MAPK pathway was involved in such colistin-induced immunomodulatory effect.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Colistin on Macrophages in Rats by Activating the p38/MAPK Pathway

et al. 2019

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“…The epithelial cells demonstrated a decrease in mucin secretion and expression of inflammatory cytokines after the therapy by roxithromycin 17 . Relaxation in smooth muscle cells, inhibition of IL‐8 production and release, and decreases in fibroblast growth factors are also seen with macrolide use in in vitro studies 5,16,17 …”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory mediator‐related investigations in patients with ABRS have rarely been performed and our study is the first one which evaluated the chemokine production by nasal mucosa during the therapy with Pelargonium sidoides extract. According to previous investigations, contents of nasal secretions reflects the inflammatory status of the nasal mucosa and evolution of mucosal disease 14‐16 . Nasal epithelial cells elicit their own repertoire of immune responses and actively prevent pathogens from damaging the airway.…”

Section: Discussionmentioning

confidence: 99%

“…Effects have been reported on airway secretions, inflammation, and direct effect on bacteria. The many different actions of macrolide antibiotics on cellular function, including airway epithelial cells, neutrophils, eosinophils, lymphocytes, monocytes, macrophages, fibroblasts, and vascular endothelial cells have been described 16 . The epithelial cells demonstrated a decrease in mucin secretion and expression of inflammatory cytokines after the therapy by roxithromycin 17 .…”

Section: Discussionmentioning

confidence: 99%

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Effects of Pelargonium sidoides extract vs roxithromycin on chemokine levels in nasal secretions of patients with uncomplicated acute rhinosinusitis

Perić

Kovačević

Barać

et al. 2020

Laryngoscope Investig Oto

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Background Previous investigations suggest the use of extract from the roots of Pelargonium sidoides (EPs 7630) for the therapy of uncomplicated rhinosinusitis. The aim of this prospective study was to compare the effects of herbal drug EPs 7630 and antibiotic roxithromycin on chemokine production in nasal mucosa and clinical parameters in patients with uncomplicated acute bacterial rhinosinusitis (ABRS). Methods Seventy‐eight ABRS patients were divided into 26 patients receiving EPs 7630 tablets, 3 × 20 mg/day per os (group 1), 26 patients receiving roxithromycin tablets, 2 × 150 mg/day per os (group 2), both for 10 days, and 26 patients who received no therapy (Control group). We measured chemokine levels in nasal secretions by flow cytometry and assessed clinical parameters on day 0 and day 10 of investigation. Results EPs 7630 increased concentrations of MCP‐1 (P = .001) and IP‐10 (P = .049) and decreased levels of MIP‐1α (P < .001), ENA‐78 (P < .001), and IL‐8 (P < .001). Roxithromycin increased levels of IP‐10 (P = .049) and decreased levels of MCP‐1 (P < .001), MIP‐1α (P < .016), ENA‐78 (P < .001), and IL‐8 (P < .001). Comparison of the non‐treated patients' group with groups 1 and 2 revealed significant improvement of all clinical parameters in treated patients (P < .001), but therapy with roxithromycin resulted in better improvement in nasal symptoms and endoscopic findings than therapy with EPs 7630. Conclusion Our results suggest the presence of similar modulatory effects of both therapies on production of chemokines that regulate the function of neutrophils and monocytes in nasal mucosa. Roxithromycin shows better clinical efficacy than EPs 7630 in patients with uncomplicated ABRS. Level of Evidence 1b.

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“…In contrast, some antibiotics have shown immunomodulatory properties ( Ruh et al, 2017 ) such as macrolides which suppress inflammatory cytokines ( Hoyt and Robbins, 2001 ; Amsden, 2005 ). Azithromycin has been particularly studied in CF and is routinely used for its immunomodulating effects, having shown to reduce exacerbation frequency and slightly improve lung function when taken continuously ( Bush and Rubin, 2003 ; Southern and Barker, 2004 ; Olveira et al, 2017 ).…”

Section: Cf Airway Disease Treatments and Inflammationmentioning

confidence: 99%

The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease

2020

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Cystic Fibrosis (CF) is a recessive genetic disease due to mutations of the Cystic Fibrosis Transmembrane Conductance Regulator ( CFTR ) gene encoding the CFTR chloride channel. The ion transport abnormalities related to CFTR mutation generate a dehydrated airway surface liquid (ASL) layer, which is responsible for an altered mucociliary clearance, favors infections and persistent inflammation that lead to progressive lung destruction and respiratory failure. The inflammatory response is normally followed by an active resolution phase to return to tissue homeostasis, which involves specialized pro-resolving mediators (SPMs). SPMs promote resolution of inflammation, clearance of microbes, tissue regeneration and reduce pain, but do not evoke unwanted immunosuppression. The airways of CF patients showed a decreased production of SPMs even in the absence of pathogens. SPMs levels in the airway correlated with CF patients’ lung function. The prognosis for CF has greatly improved but there remains a critical need for more effective treatments that prevent excessive inflammation, lung damage, and declining pulmonary function for all CF patients. This review aims to highlight the recent understanding of CF airway inflammation and the possible impact of SPMs on functions that are altered in CF airways.

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Immunomodulatory Effects of Antimicrobial Drugs

Cited by 10 publications

References 86 publications

Immunomodulatory Effects of Colistin on Macrophages in Rats by Activating the p38/MAPK Pathway

Immunomodulatory Effects of Colistin on Macrophages in Rats by Activating the p38/MAPK Pathway

Effects of Pelargonium sidoides extract vs roxithromycin on chemokine levels in nasal secretions of patients with uncomplicated acute rhinosinusitis

The Role of Specialized Pro-Resolving Mediators in Cystic Fibrosis Airways Disease

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