Inhaled nebulized glatiramer acetate against Gram-negative bacteria is not associated with adverse pulmonary reactions in healthy, young adult female pigs


Autoři: Sandra M. Skovdal aff001;  Stig Hill Christiansen aff004;  Karen Singers Johansen aff005;  Ole Viborg aff006;  Niels Henrik Bruun aff007;  Søren Jensen-Fangel aff002;  Ida Elisabeth Holm aff008;  Thomas Vorup-Jensen aff004;  Eskild Petersen aff001
Působiště autorů: Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark aff001;  Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark aff002;  Interdisciplinary Nanoscience Center (iNANO), Faculty of Science and Technology, Aarhus University, Aarhus, Denmark aff003;  Biophysical Immunology Laboratory, Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark aff004;  Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark aff005;  Intensive Care Unit, Department of Anesthesiology, Aarhus University Hospital, Skejby, Denmark aff006;  Biostatistical Advisory Service (BIAS), Department of Public Health, Faculty of Health, Aarhus University, Aarhus, Denmark aff007;  Department of Pathology, Randers Regional Hospital, Randers, Denmark aff008
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223647

Souhrn

The developmental speed of new antimicrobials does not meet the emergence of multidrug-resistant bacteria sufficiently. A potential shortcut is assessing the antimicrobial activity of already approved drugs. Intrudingly, the antibacterial action of glatiramer acetate (GA) has recently been discovered. GA is a well-known and safe immunomodulatory drug particular effective against Gram-negative bacteria, which disrupts biological membranes by resembling the activity of antimicrobial peptides. Thus, GA can potentially be included in treatment strategies used to combat infections caused by multidrug-resistant Gram-negatives. One potential application is chronic respiratory infections caused by Pseudomonas aeruginosa, however the safety of GA inhalation has never been assessed. Here, the safety of inhaling nebulized GA is evaluated in a preclinical pig model. The potential side effects, i.e., bronchoconstriction, respiratory tract symptoms and systemic- and local inflammation were assessed by ventilator monitoring, clinical observation, biochemistry, flowcytometry, and histopathology. No signs of bronchoconstriction assessed by increased airway peak pressure, Ppeak, or decreased oxygen pressure were observed. Also, there were no signs of local inflammation in the final histopathology examination of the pulmonary tissue. As we did not observe any potential pulmonary side effects of inhaled GA, our preliminary results suggest that GA inhalation is safe and potentially can be a part of the treatment strategy targeting chronic lung infections caused by multidrug-resistant Gram-negative bacteria.

Klíčová slova:

Antibiotics – Antimicrobials – Gram negative bacteria – Inflammation – Inhalation – Pig models – Ventilators – Mannitol


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Článek vyšel v časopise

PLOS One


2019 Číslo 10

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