Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model.
Animals
Anti-Infective Agents
/ pharmacology
Bronchoalveolar Lavage Fluid
/ microbiology
Chemokine CXCL1
/ blood
Cytokines
/ blood
Drug Resistance, Bacterial
Interleukin-6
/ blood
Lung
/ immunology
Male
Mice
Mice, Inbred BALB C
Monoterpenes
/ pharmacology
Neutrophil Infiltration
Neutrophils
/ cytology
Pneumonia, Pneumococcal
/ drug therapy
Streptococcus pneumoniae
/ isolation & purification
Tropolone
/ analogs & derivatives
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
04
2020
accepted:
23
09
2020
entrez:
15
10
2020
pubmed:
16
10
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S. pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S. pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S. pneumoniae in the BALF and the concentration of S. pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia.
Identifiants
pubmed: 33057343
doi: 10.1371/journal.pone.0240329
pii: PONE-D-20-12596
pmc: PMC7561173
doi:
Substances chimiques
Anti-Infective Agents
0
Chemokine CXCL1
0
Cytokines
0
Interleukin-6
0
Monoterpenes
0
Tropolone
7L6DL16P1T
beta-thujaplicin
U5335D6EBI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0240329Déclaration de conflit d'intérêts
I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Eiji Kunitomo is an employee of Kobayashi Pharmaceutical, Co., Ltd. The funder provided support in the form of salaries for author EK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
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