Antimicrobial peptides CATH‐2 and LL‐37 produce no protective effect after intratracheal co‐administration with LPS in vivo
Notice bibliographique
Résumé
Background The host inflammatory response produced in bacterial pneumonia is a major contributing factor of the pathophysiologic processes observed in a respiratory infection. Antimicrobial peptides (AMPs) have been shown to possess potent broad‐spectrum antimicrobial activity as well as immunomodulatory properties. As a potential therapy for bacterial pneumonia, we have previously investigated the anti‐bacterial properties of AMPs in the presence of a pulmonary delivery agent, exogenous surfactant. To further explore the properties of these compounds, the current study evaluates the effects of AMPs with and without exogenous surfactant on pulmonary inflammation in vivo . Objective The objective of this study was to investigate the potential of two cathelicidin peptides, CATH‐2 and LL‐37 and the exogenous surfactant/cathelicidin mixture BLES+CATH‐2, to reduce the inflammatory response produced upon LPS stimulation in vivo . Hypothesis Intrapulmonary administration of AMPs, with and without exogenous surfactant, will reduce lipopolysaccharide (LPS) induced inflammation. Methods Two cathelicidin peptides, CATH‐2 and LL‐37, were used in this study. CATH‐2 was also administered in combination with bovine lipid‐extract surfactant (BLES), as previous studies have shown bactericidal activity and enhanced biophysical function of this combination in vitro . C57Bl/6 mice were anesthetized, intubated, and intratracheally instilled 2 mg/kg of LPS. Five minutes later, mice were intratracheally instilled with 50μL one of the following treatments: Sham (no LPS), Air, Saline, BLES (20 mg phospholipid/kg BW), CATH‐2 (100 μM), LL‐37 (100 μM), or BLES+CATH‐2. The mice were monitored for six hours, and were then euthanized. A FlexiVent was used to measure lung compliance, and bronchoalveolar lavage (BAL) fluid was collected in order to determine cell counts, cell differentials, protein content and inflammatory cytokine concentrations. Results Animals that were administered LPS showed a significant increase in neutrophil recruitment and lavage IL‐6 content compared to sham control. Animals treated with CATH‐2 and LL‐37 showed a significant decrease in lung compliance compared to all other treatment groups, as well as an increase in lavage protein and IL‐6 content obtained from the BAL fluid. There was no significant difference among treatment groups with respect to total cells found in the BAL fluid, or percentage of neutrophils recovered between treatment groups. Discussion The results from this experiment did not support our initial hypothesis, as CATH‐2 and LL‐37 did not reduce the inflammatory response elicited by LPS challenge, but instead produced an exacerbated inflammatory response as well as decreased lung function, as observed through a decrease in lung compliance. It is possible that at the doses utilized, the cytotoxic effects of cathelicidins contributed to the inflammatory responses observed. The addition of exogenous surfactant BLES mitigated the deleterious effects of CATH‐2 administration; however it did not affect the markers of inflammation compared to controls. Support or Funding Information Canadian Institutes of Health Research Program of Experimental Medicine Cystic Fibrosis Foundation
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».