Granulocyte Colony-Stimulating Factor (Neupogen®; Filgrastim) Accelerates Neutrophil Recovery in a Rodent Model of Sulfur Mustard-Induced Hematologic Toxicity.

Autor:	Beske PH; Battelle Biomedical Research Center, West Jefferson, Ohio, USA., Harvilchuck JA; Battelle Biomedical Research Center, West Jefferson, Ohio, USA., Gibbs ST; AmplifyBio, West Jefferson, Ohio, USA., Green CE; SRI International, Menlo Park, California, USA., Iyer L; SRI International, Menlo Park, California, USA., O'Loughlin K; SRI International, Menlo Park, California, USA., Hu TC; Biomedical Advanced Research and Development Authority, Washington, DC, USA., Nealy MS; National Institutes of Health/National Institute of Allergy and Infectious Diseases - Chemical Countermeasures Research Program, Bethesda, Maryland, USA., Platoff GE Jr; National Institutes of Health/National Institute of Allergy and Infectious Diseases - Chemical Countermeasures Research Program, Bethesda, Maryland, USA., Yeung DT; National Institutes of Health/National Institute of Allergy and Infectious Diseases - Chemical Countermeasures Research Program, Bethesda, Maryland, USA.
Jazyk:	angličtina
Zdroj:	Disaster medicine and public health preparedness [Disaster Med Public Health Prep] 2023 Dec 04; Vol. 17, pp. e550. Date of Electronic Publication: 2023 Dec 04.
DOI:	10.1017/dmp.2023.13
Abstrakt:	Objective: Evidence of myelosuppression has been negatively correlated with patient outcomes following cases of high dose sulfur mustard (SM) exposure. These hematologic complications can negatively impact overall immune function and increase the risk of infection and life-threatening septicemia. Currently, there are no approved medical treatments for the myelosuppressive effects of SM exposure. Methods: Leveraging a recently developed rodent model of SM-induced hematologic toxicity, post-exposure efficacy testing of the granulocyte colony-stimulating factor drug Neupogen® was performed in rats intravenously challenged with SM. Before efficacy testing, pharmacokinetic/pharmacodynamic analyses were performed in naïve rats to identify the apparent human equivalent dose of Neupogen® for efficacy evaluation. Results: When administered 1 d after SM-exposure, daily subcutaneous Neupogen® treatment did not prevent the delayed onset of hematologic toxicity but significantly accelerated recovery from neutropenia. Compared with SM controls, Neupogen®-treated animals recovered body weight faster, resolved toxic clinical signs more rapidly, and did not display transient febrility at time points generally concurrent with marked pancytopenia. Conclusions: Collectively, this work corroborates the results of a previous pilot large animal study, validates the utility of a rodent screening model, and provides further evidence for the potential clinical utility of Neupogen® as an adjunct treatment following SM exposure.
Databáze:	MEDLINE
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