Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes

Miyazaki, Michiko; Zaitsu, Masafumi; Honjo, Kinji; Ishii, Eiichi; Hamasaki, Yuhei

doi:10.1016/s0952-3278(03)00089-9

Cited by 14 publications

(3 citation statements)

References 33 publications

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“…It also affects leukocyte adhesion by suppressing any increase in the concentration of soluble vascular cell adhesion molecule‐1 (18). Furthermore, azithromycin reduces the concentrations of interleukin‐1β, granulocyte–macrophage colony‐stimulating factor (8) and prostaglandin E 2 through inhibition of the cyclooxygenase‐1 and cyclooxygenase‐2 pathways (59).…”

Section: Monotherapies or Combined Antibacterial And Anti‐inflammatormentioning

confidence: 99%

Periodontitis: a host‐mediated disruption of microbial homeostasis. Unlearning learned concepts

Bartold¹,

Dyke²

2013

Periodontology 2000

422

351

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New concepts evolve when existing ones fail to address known factors adequately or are invalidated by new evidence. For decades periodontitis has been considered to be caused by specific bacteria or groups of bacteria and, accordingly, treatment protocols have largely been based on anti‐infective therapies. However, close inspection of current data leads one to question whether these bacteria are the cause or the result of periodontitis. Good evidence is emerging to suggest that it is indeed the host response to oral bacteria that leads to the tissue changes noted in gingivitis. These changes lead to an altered subgingival environment that favors the emergence of ‘periodontal pathogens’ and the subsequent development of periodontitis if the genetic and external environmental conditions are favorable for disease development. Thus, it seems that it is indeed the initial early host‐inflammatory and immune responses occurring during the development of gingivitis, and not specific bacteria or their so‐called virulence factors, which determine whether periodontitis develops and progresses. In this review we consider these concepts and their potential to change the way in which we view and manage the inflammatory periodontal diseases.

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Section: Monotherapies or Combined Antibacterial And Anti‐inflammatormentioning

confidence: 99%

Periodontitis: a host‐mediated disruption of microbial homeostasis. Unlearning learned concepts

Bartold¹,

Dyke²

2013

Periodontology 2000

422

351

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“…However, the effect of AZM on neutrophils in response to mycobacteria is not well studied. Previous reports indicate that AZM modulates pathogen-exposed neutrophil inflammatory mediator production, ROS, phagocytosis, and killing (35)(36)(37)(38)(39). However, classic neutrophil innate immune processes in M. abscessus in the absence of opsonization, such as phagocytosis, ROS generation, and cytokine secretion, were unaffected by acute AZM treatment.…”

Section: Discussionmentioning

confidence: 92%

“…Azithromycin (AZM) is a macrolide antibiotic, and it is one of the few therapeutic options for NTM infections (8). In addition to its antibiotic activity, AZM displays immunomodulatory effects to alter host responses to pathogens, including increased bactericidal activity but inhibition of inflammatory cytokines, reactive oxygen species (ROS), neutrophil extracellular trap formation, and eicosanoid synthesis (31)(32)(33)(34)(35)(36)(37)(38)(39). A novel immunomodulatory activity of AZM was described by Renna et al during NTM infection, resulting in inhibition of macrophage autophagy and increased survival of M. abscessus (40), specifically by inhibiting lysosome acidification and reducing lysosomephagosome fusion.…”

mentioning

confidence: 99%

Mycobacterium abscessus Clearance by Neutrophils Is Independent of Autophagy

et al. 2020

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Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly prevalent in chronic lung disease, including cystic fibrosis, and infections are characterized by neutrophil-dominated environments. However, mechanisms of immune control are poorly understood. Azithromycin, a macrolide antibiotic with immunomodulatory effects, is used to treat M. abscessus infections. Recently, inhibition of macrophage bactericidal autophagy was described for azithromycin, which could be detrimental to the host. Therefore, we explored the role of autophagy in mycobactericidal neutrophils. Azithromycin did not affect M. abscessus-induced neutrophil reactive oxygen species formation, phagocytosis, or cytokine secretion, and neutrophils treated with azithromycin killed M. abscessus equally as well as untreated neutrophils from either healthy or cystic fibrosis subjects. One clinical isolate was killed more effectively in azithromycin-treated neutrophils, suggesting that pathogen-specific factors may interact with an azithromycin-sensitive pathway. Chloroquine and rapamycin, an inhibitor and an activator of autophagy, respectively, also failed to affect mycobactericidal activity, suggesting that autophagy was not involved. However, wortmannin, an inhibitor of intracellular trafficking, inhibited mycobactericidal activity, but as a result of inhibiting phagocytosis. The effects of these autophagy-modifying agents and azithromycin in neutrophils from healthy subjects were similar between the smooth and rough morphotypes of M. abscessus. However, in cystic fibrosis neutrophils, wortmannin inhibited killing of a rough clinical isolate and not a smooth isolate, suggesting that unique host-pathogen interactions exist in cystic fibrosis. These studies increase our understanding of M. abscessus virulence and of neutrophil mycobactericidal mechanisms. Insight into the immune control of M. abscessus may provide novel targets of therapy.

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Azithromycin in viral infections

Oliver

Hinks

2020

Reviews in Medical Virology

107

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Summary Azithromycin (AZM) is a synthetic macrolide antibiotic effective against a broad range of bacterial and mycobacterial infections. Due to an additional range of anti‐viral and anti‐inflammatory properties, it has been given to patients with the coronaviruses SARS‐CoV or MERS‐CoV. It is now being investigated as a potential candidate treatment for SARS‐CoV‐2 having been identified as a candidate therapeutic for this virus by both in vitro and in silico drug screens. To date there are no randomised trial data on its use in any novel coronavirus infection, although a large number of trials are currently in progress. In this review, we summarise data from in vitro, murine and human clinical studies on the anti‐viral and anti‐inflammatory properties of macrolides, particularly AZM. AZM reduces in vitro replication of several classes of viruses including rhinovirus, influenza A, Zika virus, Ebola, enteroviruses and coronaviruses, via several mechanisms. AZM enhances expression of anti‐viral pattern recognition receptors and induction of anti‐viral type I and III interferon responses. Of relevance to severe coronavirus‐19 disease (COVID‐19), which is characterised by an over‐exuberant innate inflammatory response, AZM also has anti‐inflammatory properties including suppression of IL‐1beta, IL‐2, TNF and GM‐CSF. AZM inhibits T cells by inhibiting calcineurin signalling, mammalian target of rapamycin activity and NFκB activation. AZM particularly targets granulocytes where it concentrates markedly in lysosomes, particularly affecting accumulation, adhesion, degranulation and apoptosis of neutrophils. Given its proven safety, affordability and global availability, tempered by significant concerns about antimicrobial stewardship, there is an urgent mandate to perform well‐designed and conducted randomised clinical trials.

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Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes

Cited by 14 publications

References 33 publications

Periodontitis: a host‐mediated disruption of microbial homeostasis. Unlearning learned concepts

Periodontitis: a host‐mediated disruption of microbial homeostasis. Unlearning learned concepts

Mycobacterium abscessus Clearance by Neutrophils Is Independent of Autophagy

Azithromycin in viral infections

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