The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study

Autor: Howard J. Huang, David E. Scherrer, Derek E. Byers, Adrian Shifren, Sharon Phillips, Delphine L. Chen, Elizabeth Arentson, Katherine J. Spayd, Debra Kemp, Jacquelyn T. Engle, Richard A. Pierce, Mario Castro, Bryan G Belikoff, Frank J. Brooks, Warren Isakow, Hideji Fujiwara
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Neutrophils
Physiology
Peptide Hormones
Peroxisome Proliferator-Activated Receptors
lcsh:Medicine
Toxicology
Pathology and Laboratory Medicine
Gastroenterology
Biochemistry
Diagnostic Radiology
Efficacy
Placebos
chemistry.chemical_compound
White Blood Cells
0302 clinical medicine
Animal Cells
Immune Physiology
Medicine and Health Sciences
Toxins
Hydroxyurea
Single-Blind Method
lcsh:Science
Tomography
Immune Response
Leukotriene E4
Innate Immune System
Multidisciplinary
medicine.diagnostic_test
Radiology and Imaging
Pulmonary Imaging
Healthy Volunteers
3. Good health
Cohort
Cytokines
Female
Adiponectin
Cellular Types
medicine.drug
Research Article
Adult
medicine.medical_specialty
Imaging Techniques
Immune Cells
Inflammatory Diseases
Toxic Agents
Bacterial Toxins
Immunology
Neuroimaging
Placebo
Research and Analysis Methods
03 medical and health sciences
Young Adult
Signs and Symptoms
Adipokines
Diagnostic Medicine
Internal medicine
medicine
Humans
Inflammation
Blood Cells
Arachidonate 5-Lipoxygenase
Pioglitazone
business.industry
lcsh:R
Biology and Life Sciences
Zileuton
Cell Biology
Molecular Development
Hormones
Computed Axial Tomography
Endotoxins
030104 developmental biology
Bronchoalveolar lavage
030228 respiratory system
chemistry
Immune System
Positron-Emission Tomography
lcsh:Q
Thiazolidinediones
business
Positron Emission Tomography
Neuroscience
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 2, p e0191783 (2018)
ISSN: 1932-6203
Popis: BACKGROUND:Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. METHODS:For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). RESULTS:Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p
Databáze: OpenAIRE
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