Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial

Background Interleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasm...

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Veröffentlicht in:Critical care (London, England) Jg. 26; H. 1; S. 164 - 8
Hauptverfasser: Boyle, Andrew James, Ferris, Peter, Bradbury, Ian, Conlon, John, Shankar-Hari, Manu, Rogers, Angela J., O’Kane, Cecilia M., McAuley, Daniel F.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 07.06.2022
BioMed Central Ltd
Springer Nature B.V
BMC
Schlagworte:
Acute respiratory distress syndrome
Biological markers
Carrier Proteins
Clinical trials
Complications and side effects
Confidence intervals
Critical care
Critical Care Medicine
Cytokines
Drug therapy
Emergency Medicine
Health aspects
Humans
Inflammasome
Inflammasomes
Intensive
Interleukin-18
Medicine
Medicine & Public Health
Mortality
Patient outcomes
Patients
Personalised medicine
Personalized medicine in the ICU
Plasma
Precision medicine
Regression analysis
Respiratory distress syndrome
Respiratory Distress Syndrome - drug therapy
Risk factors
Sepsis
Simvastatin
Simvastatin - pharmacology
Simvastatin - therapeutic use
Statins
Testing
United Kingdom
United Kingdom > UK
Germany
Acute respiratory distress syndrome
Inflammasome
Personalised medicine
Interleukin-18
Simvastatin
ISSN:1364-8535, 1466-609X, 1364-8535, 1466-609X, 1366-609X
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Zusammenfassung:Background Interleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasma IL-18. Methods In this secondary analysis of the HARP-2 study, we compared 28-day mortality and response to simvastatin according to baseline plasma IL-18 using cox proportional hazards analysis. Separately, monocyte-derived macrophages from healthy volunteers were pre-incubated with simvastatin or rosuvastatin before stimulation with ATP and LPS, and the effect on secreted IL-18 and IL-1β compared. Results 511 patients from HARP-2 had available data. High baseline plasma IL-18 (≥ 800 pg/ml) was associated with increased 28-day mortality (high IL-18 30.6% vs. low IL-18 17.5%; HR 1.89 [95% CI 1.30–2.73]; p  = 0.001). Allocation to simvastatin in patients with high baseline plasma IL-18 was associated with a lower probability of 28-day mortality compared with placebo (24.0% vs 36.8%; p  = 0.01). Finally, simvastatin, but not rosuvastatin, reduced stimulated macrophage secretion of IL-18 and IL-1β. Conclusion In patients with high baseline plasma IL-18, simvastatin is associated with a higher probability of survival, and this effect may be due to reduced inflammasome activation. These data suggest that baseline plasma IL-18 may allow a personalised treatment approach by identifying patients with ARDS who could benefit from simvastatin therapy.
Bibliographie:ObjectType-Article-1
ObjectType-Evidence Based Healthcare-3
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ObjectType-Undefined-3
ISSN:1364-8535
1466-609X
1364-8535
1466-609X
1366-609X
DOI:10.1186/s13054-022-04025-w