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Effects of G-CSF on systemic inflammation, coagulation and platelet activation in patients with acute myocardial
Birgit A Steppich1, Gabriele Demetz, Stefanie Schulz
11. Medizinische Klinik, Klinikums rechts der Isar der Technischen Universität München, Ismaninger Str 22, 81675 München, Germany.
Insights
Granulocyte-colony stimulating factor (G-CSF) treatment in acute myocardial infarction (AMI) patients increased TNF-α and CRP levels. However, G-CSF did not activate coagulation or platelet function in this study.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Immunology
Background:
- The REVIVAL-2 trial investigated granulocyte-colony stimulating factor (G-CSF) in patients with acute myocardial infarction (AMI).
- This substudy focused on G-CSF's effects on systemic inflammation, coagulation, and platelet activation post-AMI.
- Patients received either G-CSF or placebo after mechanical reperfusion.
Purpose of the Study:
- To evaluate the impact of G-CSF on inflammatory markers, coagulation activation, and platelet activation in AMI patients.
- To determine if G-CSF influences systemic inflammatory and procoagulant responses.
- To assess G-CSF's effect on platelet activation markers.
Main Methods:
- Prospective, randomized, double-blind, placebo-controlled substudy.
- Measurement of circulating cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12, TNF-α) and C-reactive protein (CRP).
- Assessment of coagulation activation via prothrombin fragment F1+2 and Tissue Factor activity.
- Flow cytometry analysis of platelet activation markers (PAC-1, P-selectin, CD40L).
Main Results:
- G-CSF administration led to significantly elevated TNF-α and CRP levels compared to placebo after 5 days.
- No significant differences were observed in other measured cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) between groups.
- Circulating prothrombin fragments F1+2, Tissue Factor activity, and platelet activation markers remained comparable in both G-CSF and placebo groups.
Conclusions:
- G-CSF treatment in AMI patients is associated with increased pro-inflammatory markers TNF-α and CRP.
- G-CSF did not induce systemic coagulation activation in this patient cohort.
- Platelet activation was not significantly affected by G-CSF treatment in AMI patients.
Introduction:
In the prospective, randomised, double-blind, placebo-controlled Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells (REVIVAL)-2 trial patients with acute myocardial infarction (AMI) and successful mechanical reperfusion received granulocyte-colony stimulating factor (G-CSF, 10 μg/kg KG s.c.) or placebo for 5 days. Aim of this substudy was to assess the impact of G-CSF on systemic inflammatory and procoagulant responses and platelet activation.
Methods And Results:
Before and five days after G-CSF (n=56) or placebo (n=58) circulating cytokine concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12 and Tumor-Necrosis Factor-α (TNF-α were measured. Prothrombin fragment F1+2 and Tissue Factor activity served as a measure for activated coagulation. Platelet activation was characterized by cell surface expression of the activated fibrinogen receptor (PAC-1), P-selectin and CD40L by flow cytometry. Administration of G-CSF was associated with elevated TNF-α and CRP concentrations compared to the placebo group after 5 days. Other cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) were comparable after treatment with G-SCF or placebo. Similarly, circulating prothrombin fragments F1+2, TF activity and platelet activation did not differ in both groups.
Conclusion:
Treatment with G-CSF in patients with AMI was associated with enhanced proinflammatory TNF-α and CRP levels but no activation of coagulation.
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