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Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute
Marco Giuseppe Del Buono1,2, Juan Ignacio Damonte1,3, Cory R Trankle1
1Division of Cardiology, Department of Internal Medicine, VCU Pauley Heart Center, Virginia Commonwealth University, West Hospital, West Wing 5-020, 1200 E Broad Street, P.O. Box 980204, Richmond, VA, 23298, USA.
Insights
Anakinra, an interleukin-1 receptor antagonist, significantly reduced white blood cell and neutrophil counts in ST-elevation myocardial infarction patients. This IL-1 blockade accelerates leukocytosis resolution, potentially improving clinical outcomes.
Area of Science:
- Cardiology
- Immunology
- Hematology
Background:
- Leukocytosis is common in ST-elevation myocardial infarction (STEMI) and linked to poor prognosis.
- Interleukin-1 beta (IL-1β) influences white blood cell production.
- Pre-clinical data suggest anakinra, an IL-1 receptor antagonist, may reduce leukocytosis in myocardial infarction.
Purpose of the Study:
- To investigate the effect of IL-1 blockade with anakinra on leukocyte counts in STEMI patients.
- To determine if anakinra influences white blood cell and differential counts post-STEMI.
Main Methods:
- Retrospective analysis of 99 STEMI patients from a clinical trial.
- Comparison of anakinra (n=64) versus placebo (n=35) treatment groups.
- White blood cell and differential counts assessed at baseline, 72 hours, 14 days, and 3 months.
Main Results:
- Anakinra significantly reduced total white blood cell count by 35% vs. 21% in placebo after 72 hours (P=0.008).
- Anakinra led to a greater reduction in absolute neutrophil count (48% vs. 27%, P=0.004).
- Anakinra increased absolute eosinophil count (50% vs. 0%, P=0.022), with effects persisting at 14 days but not at 3 months.
Conclusions:
- IL-1 blockade with anakinra accelerates the resolution of leukocytosis and neutrophilia in STEMI patients.
- This modulation of leukocyte counts may be a mechanism for improved clinical outcomes with IL-1 blockade.
Abstract:
Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-β regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (- 35% [- 48 to - 24] vs. - 21% [- 34 to - 10], P = 0.008), absolute neutrophil count (- 48% [- 60 to - 22] vs. - 27% [- 46 to - 5], P = 0.004) and to an increase in absolute eosinophil count (+ 50% [0 to + 100] vs. 0% [- 50 to + 62], P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.
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