Anti-inflammatory properties of antibiotics other than macrolides

Rubin, Bruce K.; Henke, Markus O.; Dalhoff, A.

doi:10.1007/3-7643-7310-5_16

Cited by 3 publications

(4 citation statements)

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“…Fluoroquinolones are able to modify transepithelial Cl secretion, phagocyte functions, T-cell responses, and cytokine production (128,160,242). Moxifloxacin and ciprofloxacin dose dependently decreased IFN-␥ and IL-4 expression by T cells in vitro (324).…”

Section: Quinolonesmentioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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SUMMARY Macrolides have diverse biological activities and an ability to modulate inflammation and immunity in eukaryotes without affecting homeostatic immunity. These properties have led to their long-term use in treating neutrophil-dominated inflammation in diffuse panbronchiolitis, bronchiectasis, rhinosinusitis, and cystic fibrosis. These immunomodulatory activities appear to be polymodal, but evidence suggests that many of these effects are due to inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and nuclear factor kappa B (NF-κB) activation. Macrolides accumulate within cells, suggesting that they may associate with receptors or carriers responsible for the regulation of cell cycle and immunity. A concern is that long-term use of macrolides increases the emergence of antimicrobial resistance. Nonantimicrobial macrolides are now in development as potential immunomodulatory therapies.

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Section: Quinolonesmentioning

confidence: 99%

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

2010

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“…Almost any class of antibacterial exerts immunomodulatory effects. Macrolides and fluoroquinolones exert their immunomodulatory effects via modulations of transcription factors, such as NF-B, activator protein 1, NF-interleukin-6, and nuclear factor of activated T cells, as well as cyclic AMP, leading to the downregulation of proinflammatory and upregulation of colony-stimulating factors (327)(328)(329)(330)(331)(332). Beta-lactams conjugate to inflammation-promoting cytokines, thus reducing their inflammatory activity (333)(334)(335).…”

Section: The Cf Inflammasomementioning

confidence: 99%

“…Macrolides were shown to exert beneficial clinical effects on CF patients with P. aeruginosa lung infection (286,331,332), despite their lack of in vitro activity against P. aeruginosa. Fluoroquinolones are known to modulate immunoresponses, in particular in preclinical infection models of and in patients with respiratory tract infections (328)(329)(330); however, a contribution of immunomodulatory activities of fluoroquinolones to clinical or bacteriological success has not yet been proven. Likewise, the impact of immunomodulatory activities of ␤-lactams and aminoglycosides on successful treatment of respiratory tract infections has not been studied.…”

Section: The Cf Inflammasomementioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Dalhoff¹

2014

Clin Microbiol Rev

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SUMMARY Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.

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“…The removal or reduction/disruption of host-associated microorganisms using antibiotics is a common approach (reviewed in [26]) that has been used to study, for example, effects on host immunity, metabolism and disease [38][39][40]. However, the key question which arises from their use is: how do we decouple the potential direct physical/chemical effects of antimicrobials on host performance (e.g [41,42]) from indirect, microbially-mediated effects? This is a complex and ongoing issue as different antimicrobials cause vastly different effects, both within the host and on its microbiome [43,44].…”

Section: Introductionmentioning

confidence: 99%

Disentangling direct vs indirect effects of microbiome manipulations in a habitat-forming marine holobiont

McGrath

Lema

Egan

et al. 2023

Preprint

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Background Host-associated microorganisms are now recognised as being critical for eukaryotic host functioning; however, most studies to date have focused on descriptive approaches or have used model systems, usually in the laboratory, to understand host-microbiome interactions. To advance our understanding of host-microbiome interactions and their wider ecological impacts, we need (i) robust experimental frameworks to explore causality in host-microbiome interactions and (ii) protocols that apply to model systems but also to often highly diverse natural systems. Results We used a dominant habitat-forming seaweed, Hormosira banksii, to explore a widely applicable framework for experimentally testing host-microbiome interactions. The experimental protocols were particularly designed to try and disentangle microbially-mediated effects on hosts from direct effects on hosts associated with the methods employed to manipulate host-microbiota. This was done through a combination of antimicrobial treatments, which have widespread use in holobiont research, and inoculations, in mesocosms and in the field. Three different antibiotic treatments were used to disrupt seaweed-associated microbial communities to test whether such microbiome disturbances would negatively affect host performance. Responses of microbiomes to these disturbances were complex and differed substantially among treatments. However, by comparing the temporal sequence of antibiotic treatments, changes in microbial diversity, and decreases in host performance, a consistent effect of the microbiome on host performance was observed in some treatments. To further test these effects, we used gene sequencing to identify microbial taxa that were both correlated and uncorrelated with poor host performance following antibiotic treatment. These were then isolated and used in inoculation experiments, independently or in combination with the previously used antibiotic treatments. Negative effects on host condition were strongest where specific microbial disturbances (by particular antimicrobials) were combined with inoculations of strains correlated with poor host performance. For these treatments, negative host effects persisted the entire experimental period (12 days), even though treatments were only applied at the beginning of the experiment. Host condition recovered in all other treatments. Conclusions This experimental framework allows for causal relationships to be determined within ecologically important holobionts. This should allow for better predictions of how these systems will respond to, and potentially mitigate, environmental disturbances in their natural context.

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Anti-inflammatory properties of antibiotics other than macrolides

Cited by 3 publications

References 108 publications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications

Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients

Disentangling direct vs indirect effects of microbiome manipulations in a habitat-forming marine holobiont

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