دورية أكاديمية
Plerixafor for pathogen‐agnostic treatment in murine thigh infection and zebrafish sepsis
| العنوان: | Plerixafor for pathogen‐agnostic treatment in murine thigh infection and zebrafish sepsis |
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| المؤلفون: | Martin O. Evans, Darren M. Smith, Adrian T. Kress, Robert J. Nadeau, Daniel J. Selig, Diana Caridha, Ratanachat Racharaks, Thomas Langowski, Michael S. Madejczyk, Chance Carbaugh, David Saunders, Mark Widder, Jason De Meese, Patricia J. Lee, Jesse P. DeLuca |
| المصدر: | Clinical and Translational Science, Vol 17, Iss 7, Pp n/a-n/a (2024) |
| بيانات النشر: | Wiley, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Public aspects of medicine |
| مصطلحات موضوعية: | Therapeutics. Pharmacology, RM1-950, Public aspects of medicine, RA1-1270 |
| الوصف: | Abstract Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen‐agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator‐led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)‐induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U‐shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen‐agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1752-8062 1752-8054 |
| Relation: | https://doaj.org/toc/1752-8054; https://doaj.org/toc/1752-8062 |
| DOI: | 10.1111/cts.13876 |
| URL الوصول: | https://doaj.org/article/e1f253fa61f04f4a85dd315fe4e40e06 |
| رقم الأكسشن: | edsdoj.1f253fa61f04f4a85dd315fe4e40e06 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17528062 17528054 |
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| DOI: | 10.1111/cts.13876 |