Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome

A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated...

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Published inCritical care medicine Vol. 47; no. 8; p. 1089
Main Authors Rogers, Angela J, Guan, Jiazhen, Trtchounian, Anna, Hunninghake, Gary M, Kaimal, Rajani, Desai, Manisha, Kozikowski, Lori-Ann, DeSouza, Lesley, Mogan, Susan, Liu, Kathleen D, Matthay, Michael A, Steingrub, Jay, Wheeler, Art, Yoon, Joo Heon, Nakahira, Kiichi, Choi, Augustine M, Baron, Rebecca M
Format Journal Article
LanguageEnglish
Published United States 01.08.2019
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Abstract A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. Retrospective analysis of randomized controlled clinical trial. Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however. Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.
AbstractList A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin exposure increases both inflammasome activation and lung injury in mouse models. We tested whether randomization to statin therapy correlated with increased interleukin-18 in the ARDS Network Statins for Acutely Injured Lungs from Sepsis trial. Retrospective analysis of randomized controlled clinical trial. Multicenter North American clinical trial, the ARDS Network Statins for Acutely Injured Lungs from Sepsis. Six hundred eighty-three subjects with infection-related acute respiratory distress syndrome, representing 92% of the original trial population. Random assignment of rosuvastatin or placebo for up to 28 days or 3 days after ICU discharge. We measured plasma interleukin-18 levels in all Statins for Acutely Injured Lungs from Sepsis patients with sample available at day 0 (baseline, n = 683) and day 3 (after randomization, n = 588). We tested the association among interleukin-18 level at baseline, rising interleukin-18, and the impact of statin therapy on 60-day mortality, adjusting for severity of illness. Baseline plasma interleukin-18 level greater than or equal to 800 pg/mL was highly associated with 60-day mortality, with a hazard of death of 2.3 (95% CI, 1.7-3.1). Rising plasma interleukin-18 was also associated with increased mortality. For each unit increase in log2 (interleukin-18) at day 3 compared with baseline, the hazard of death increased by 2.3 (95% CI, 1.5-3.5). Subjects randomized to statin were significantly more likely to experience a rise in plasma interleukin-18 levels. Subjects with acute kidney injury, shock, low baseline interleukin-18, and those not receiving systemic corticosteroids were more likely to experience rising interleukin-18. Randomization to statin therapy was associated with rising in interleukin-18 in all of those subsets, however. Elevated baseline plasma interleukin-18 was associated with higher mortality in sepsis-induced acute respiratory distress syndrome. A rise in plasma interleukin-18 was also associated with increased mortality and was more common in subjects randomized to statin therapy in this clinical trial.
Author Matthay, Michael A
Yoon, Joo Heon
Kozikowski, Lori-Ann
Choi, Augustine M
Hunninghake, Gary M
Mogan, Susan
Nakahira, Kiichi
Baron, Rebecca M
Desai, Manisha
Liu, Kathleen D
Rogers, Angela J
DeSouza, Lesley
Guan, Jiazhen
Kaimal, Rajani
Steingrub, Jay
Trtchounian, Anna
Wheeler, Art
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  organization: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, TN
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  surname: Liu
  fullname: Liu, Kathleen D
  organization: Department of Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA
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References 31833991 - Crit Care Med. 2020 Jan;48(1):e78
32219440 - QJM. 2020 Jul 1;113(7):509-510
31833990 - Crit Care Med. 2020 Jan;48(1):e77-e78
31305304 - Crit Care Med. 2019 Aug;47(8):1161-1163
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Snippet A high plasma level of inflammasome mediator interleukin-18 was associated with mortality in observational acute respiratory distress syndrome cohorts. Statin...
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StartPage 1089
SubjectTerms Acute Lung Injury - immunology
Adult
Female
Humans
Intensive Care Units
Interleukin-18 - blood
Male
Middle Aged
Pulmonary Alveoli - physiopathology
Respiratory Distress Syndrome - immunology
Respiratory Distress Syndrome - mortality
Retrospective Studies
Sepsis - blood
Sepsis - mortality
Title Association of Elevated Plasma Interleukin-18 Level With Increased Mortality in a Clinical Trial of Statin Treatment for Acute Respiratory Distress Syndrome
URI https://www.ncbi.nlm.nih.gov/pubmed/31206358
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