Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Steel, Helen C.; Theron, Annette J.; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

doi:10.1155/2012/584262

Cited by 94 publications

(99 citation statements)

References 228 publications

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“…Binding to the A site prevents addition of an incoming amino acid-charged tRNA to the nascent polypeptide chain, aborting polypeptide growth (15). In addition to their direct antibacterial effect, macrolides are immunomodulators, presenting anti-inflammatory activities on cells of the innate and adaptive immunity and on structural cells (16)(17)(18). On airway epithelia, macrolides positively regulate tight junctions (19) and suppress the activation of NF-B, Sp1, and AP-1, leading to a reduction of proinflammatory cytokines (20)(21)(22)(23)(24)(25).…”

Section: N Ontypeable (Noncapsulated) Haemophilus Influenzae (Nthi)mentioning

confidence: 99%

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Euba

Moleres

Viadas

et al. 2015

Antimicrob Agents Chemother

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Section: N Ontypeable (Noncapsulated) Haemophilus Influenzae (Nthi)mentioning

confidence: 99%

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Euba

Moleres

Viadas

et al. 2015

Antimicrob Agents Chemother

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“…Patients with chronic P. aeruginosa lung infection are often treated with AZM because of its anti-pseudomonal and immunomodulatory properties [16,17]. Unfortunately, there is a number of patients that do not benefit from AZM therapy or that show adverse effects to the drug [18].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

et al. 2018

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Background: Cystic fibrosis (CF) lung infection is a complex condition where opportunistic pathogens and defective immune system cooperate in developing a constant cycle of infection and inflammation. The major pathogen, Pseudomonas aeruginosa, secretes a multitude of virulence factors involved in host immune response and lung tissue damage. In this study, we examined the possible anti-inflammatory effects of molecules inhibiting P. aeruginosa virulence factors.Methods: Pyocyanin, pyoverdine and proteases were measured in bacterial culture supernatant from different P. aeruginosa strains. Inhibition of virulence factors by sub-inhibitory concentrations of clarithromycin and by protease inhibitors was evaluated. Lung inflammatory response was monitored by in vivo bioluminescence imaging in wild-type and CFTR-knockout mice expressing a luciferase gene under the control of a bovine IL-8 promoter.Results: The amount of proteases, pyocyanin and pyoverdine secreted by P. aeruginosa strains was reduced after growth in the presence of a sub-inhibitory dose of clarithromycin. Intratracheal challenge with culture supernatant containing bacteria-released products induced a strong IL-8-mediated response in mouse lungs while lack of virulence factors corresponded to a reduction in bioluminescence emission. Particularly, sole inactivation of proteases by inhibitors Ilomastat and Marimastat also resulted in decreased lung inflammation.Conclusions: Our data support the assumption that virulence factors are involved in P. aeruginosa pro-inflammatory action in CF lungs; particularly, proteases seem to play an important role. Inhibition of virulence factors production and activity resulted in decreased lung inflammation; thus, clarithromycin and protease inhibitors potentially represent additional therapeutic therapies for P. aeruginosa-infected patients.

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“…The macrolide antibiotic tilmicosin is a tylosin-derivative being used in treatment of respiratory diseases in different animal species. Despite the inflammatory modulating potential of macrolide members, particularly that of erythromycin, has been reported (Labro, 1998;Steel et al, 2012), however, there is no, at least for our information, any data reported about antipyretic potential of this drug group.…”

Section: Discussionmentioning

confidence: 64%

In vivo assessment of the antipyretic activity of tilmicosin

El-Mahmoudy¹,

Gheith²,

Elmajdoub³

et al. 2018

Afr. J. Pharm. Pharmacol.

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The aim of the present study was to assess the antipyretic activity of the macrolide antibiotic, tilmicosin, at dose levels of 20 and 40 mg/kg of body weight, subcutaneously, in Brewer's yeast-induced fever model in mice. Pyrexia was induced by subcutaneous injection of 20 mL/kg of 20% (w/v) Brewer's yeast suspension into the animal's scruff region. Eighteen hours later, feverish animals were treated with either tilmicosin or acetylsalicylic acid (200 mg/kg injectable solution, subcutaneously) or vehicle; and rectal temperatures were evaluated at 1, 2, 3, 4 and 5 h post-treatment using digital thermometers. Tilmicosin showed dose-dependent significant decrease in the elevated body temperature of mice that remained sustained throughout the tested time points from 1 to 5 h in the used model. Both small and large dose levels showed a significant inhibition of elevated body temperature when compared with the corresponding febrile controls (37.65 ± 0.04 vs. 38.41 ± 0.08°C and 37.44 ± 0.04 vs. 38.44 ± 0.04, after 1 h; 37.19 ± 0.04 vs. 38.41 ± 0.08°C and 36.80 ± 0.03 vs. 38.44 ± 0.04°C after 5 h, respectively). These activities were standardized as 38.0 and 51.59% and 47.9 and 66.43% after 5 h, respectively, compared to that of the standard antipyretic and acetylsalicylic acid (200 mg/kg of body weight, subcutaneously). These results may indicate that tilmicosin, in addition to its well established antibacterial activity, possesses significant antipyretic activity that may be beneficial in symptomatic relief when it is used in therapy of infectious disease conditions and inflammatory disorders.

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Pathogen- and Host-Directed Anti-Inflammatory Activities of Macrolide Antibiotics

Cited by 94 publications

References 228 publications

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection

Inhibition of Pseudomonas aeruginosa secreted virulence factors reduces lung inflammation in CF mice

In vivo assessment of the antipyretic activity of tilmicosin

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