Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Mu, Xiaoqin; Ubagai, Tsuneyuki; Kikuchi-Ueda, Takane; Tansho-Nagakawa, Shigeru; Nakano, Ryuichi; Kikuchi, Hirotoshi; Ono, Yasuo

doi:10.1159/000358818

Cited by 11 publications

(15 citation statements)

References 58 publications

(28 reference statements)

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“…Although not a first line treatment for CD, rifampin is an effective second line treatment for CD [49]. In one study of 180 isolates of pathogenic CD from Canada and Italy, only 10% were resistant to rifampin [50]. The author has seen only 2 case of CD develop in over 800 patients treated with clindamycin and rifampin.…”

Section: Clostridium Difficile Colitismentioning

confidence: 99%

Why rifampin (rifampicin) is a key component in the antibiotic treatment of hidradenitis suppurativa: a review of rifampin's effects on bacteria, bacterial biofilms, and the human immune system

Scheinfeld¹

2016

Dermatology Online Journal

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Section: Clostridium Difficile Colitismentioning

confidence: 99%

Why rifampin (rifampicin) is a key component in the antibiotic treatment of hidradenitis suppurativa: a review of rifampin's effects on bacteria, bacterial biofilms, and the human immune system

Scheinfeld¹

2016

Dermatology Online Journal

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“…As an example, in vitro studies have shown that rifampicin results in less release of LTA and pro-inflammatory compounds from Streptococcus pneumoniae than the β-lactam antibiotics ceftriaxone or meropenem, despite similar bacterial killing effects 14 . Furthermore, rifampicin may reduce the inflammatory response by down-regulating the expression of pro-inflammatory pattern recognition receptors 15 . The killing of S. pneumoniae commences instantly after therapeutic drug concentrations are achieved.…”

Section: Introductionmentioning

confidence: 99%

Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial

Groeneveld

Reyden

Joosten

et al. 2019

Journal of Antimicrobial Chemotherapy

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Background The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with β-lactam antibiotics. Objectives We hypothesized that non-lytic rifampicin compared with lytic β-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia. Methods In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and β-lactam compared with treatment with β-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22). Results Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups. Conclusions The PRISTINE study demonstrated the feasibility of adding rifampicin to β-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.

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“…In addition to these antimicrobial properties, their therapeutic efficacies as anti-inflammatory agents have also been demonstrated in patients with chronic rhinosinusitis [3], diffuse panbronchiolitis [4], chronic obstructive pulmonary disease [5], and cystic fibrosis [6]. According to several in vitro studies, macrolide antibiotics, such as clarithromycin, azithromycin, and erythromycin, suppress the production of proinflammatory cytokines from leukocytes and thus exert immunomodulatory effects [7,8,9]. In previous in vivo studies in humans and experimental animal models, macrolide antibiotics have also been effective in the treatment of atopic dermatitis or bronchial asthma [10,11].…”

Section: Introductionmentioning

confidence: 99%

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Kazama¹,

Saito²,

Baba³

et al. 2016

Chemotherapy

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Background: Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect. Methods: Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane. Results: Clarithromycin (10 and 100 μM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-γ-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. Conclusions: This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.

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Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes

Cited by 11 publications

References 58 publications

Why rifampin (rifampicin) is a key component in the antibiotic treatment of hidradenitis suppurativa: a review of rifampin's effects on bacteria, bacterial biofilms, and the human immune system

Why rifampin (rifampicin) is a key component in the antibiotic treatment of hidradenitis suppurativa: a review of rifampin's effects on bacteria, bacterial biofilms, and the human immune system

Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

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