Abstract | BACKGROUND: METHODS: RESULTS: Treatment with ibrutinib prior to and after intranasal LTA instillation reduced alveolar macrophage activation, neutrophil influx, cytokine release and plasma leakage into the lung. Postponed treatment with ibrutinib supplementing antibiotic therapy during ongoing pneumococcal pneumonia did not impair bacterial killing in lung, blood and spleen. In this setting, ibrutinib reduced alveolar macrophage and systemic neutrophil activation and substantially diminished further monocyte and neutrophil influx in the lung. In vitro, ibrutinib inhibited macrophage TNF secretion and neutrophil activation upon LTA and pneumococcal stimulation. CONCLUSIONS:
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Authors | Alexander P de Porto, Zhe Liu, Regina de Beer, Sandrine Florquin, Onno J de Boer, Rudi W Hendriks, Tom van der Poll, Alex F de Vos |
Journal | Molecular medicine (Cambridge, Mass.)
(Mol Med)
Vol. 25
Issue 1
Pg. 3
(01 15 2019)
ISSN: 1528-3658 [Electronic] England |
PMID | 30646846
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Anti-Inflammatory Agents
- Lipopolysaccharides
- Piperidines
- Protein Kinase Inhibitors
- Pyrazoles
- Pyrimidines
- Teichoic Acids
- ibrutinib
- lipoteichoic acid
- Ceftriaxone
- Agammaglobulinaemia Tyrosine Kinase
- Btk protein, mouse
- Adenine
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Topics |
- Adenine
(analogs & derivatives)
- Agammaglobulinaemia Tyrosine Kinase
(antagonists & inhibitors)
- Animals
- Anti-Bacterial Agents
(therapeutic use)
- Anti-Inflammatory Agents
(therapeutic use)
- Bronchoalveolar Lavage Fluid
(cytology)
- Ceftriaxone
(therapeutic use)
- Lipopolysaccharides
- Lung
(drug effects, immunology)
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Myeloid Cells
(drug effects, immunology)
- Piperidines
- Pneumonia, Pneumococcal
(drug therapy, immunology)
- Protein Kinase Inhibitors
(therapeutic use)
- Pyrazoles
(therapeutic use)
- Pyrimidines
(therapeutic use)
- Teichoic Acids
|