Journal
PHARMACEUTICALS
Volume 15, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ph15030287
Keywords
lung injury; endotoxin; cytokines; cytokine receptors; peptide; mice
Categories
Funding
- Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan [110-wf-eva-30, 111-wf-eva-12]
- Ministry of Science and Technology, Taiwan [MOST 107-2314-B-038-039-MY3, MOST 110-2314-B-038-103-MY2]
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This study compares the therapeutic efficacy of KCF18 and SEM18 on endotoxin-induced lung injury and finds that single cytokine TNF-alpha inhibition can achieve similar therapeutic effects to the inhibition of triple cytokines TNF-alpha, IL-1 beta, and IL-6 in alleviating lung injury in the early phase of endotoxemia.
Endotoxemia induces lung injury. We assessed the therapeutic efficacy between triple cytokine (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], and IL-6) inhibition (mediated by KCF18 peptide) and single cytokine (TNF-alpha) inhibition (mediated by SEM18 peptide) on alleviating lung injury in the early phase of endotoxemia. Mice receiving endotoxin (Endo group), endotoxin plus KCF18 (EKCF group), or endotoxin plus SEM18 (ESEM) were monitored and euthanized at 24 h after endotoxin. Our data demonstrated altered lung function (decreases in tidal volume, minute ventilation, and dynamic compliance; and by contrast, increases in airway resistance and end expiration work) and histology (increases in injury scores, leukocyte infiltration, vascular permeability, and tissue water content) in the Endo group with significant protection observed in the EKCF and ESEM groups (all p < 0.05). Levels of inflammation (macrophage activation and cytokine upregulations), oxidation (lipid peroxidation), necroptosis, pyroptosis, and apoptosis in EKCF and ESEM groups were comparable and all were significantly lower than in the Endo group (all p < 0.05). These data demonstrate that single cytokine TNF-alpha inhibition can achieve therapeutic effects similar to triple cytokines TNF-alpha, IL-1 beta, and IL-6 inhibition on alleviating endotoxin-induced lung injury, indicating that TNF-alpha is the major cytokine in mediating lung injury in the early phase of endotoxemia.
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