Related Experiment Videos
Proinflammatory cytokines mediate the systemic inflammatory response associated with high-dose cytarabine treatment
1Department of Pediatrics, Göteborg University, Göteborg, Sweden.
Insights
High-dose cytarabine treatment can trigger a cytokine release syndrome in children, characterized by fever and inflammation. This study investigated the specific cytokine profiles associated with these reactions.
Area of Science:
- Pediatric Oncology
- Immunology
- Pharmacology
Background:
- High-dose cytarabine (ara-C) therapy in children with hematological malignancies can cause acute febrile reactions.
- Symptoms resemble systemic inflammatory response syndrome (SIRS), suggesting a role for cytokines.
Purpose of the Study:
- To investigate plasma levels of proinflammatory cytokines during high-dose cytarabine treatment in pediatric patients.
- To understand the cytokine dynamics underlying the cytarabine-induced febrile reaction.
Main Methods:
- Sixteen children receiving high-dose cytarabine (2 g/m(2)) for hematological malignancies were monitored.
- Plasma cytokine levels (TNF-α, IFN-γ, IL-1γ, IL-6, IL-8, IL-10, IL-1ra) were measured pre-treatment and at 12, 36, and 60 hours post-treatment, and upon fever onset.
Main Results:
- Thirteen of 16 patients developed fever, with a median onset at 30 hours.
- Elevated tumor necrosis factor-alpha (TNF-α) was observed at 12 hours, followed by increased IL-6, IFN-γ, and IL-1ra peaking at fever onset.
- Interleukin-10 (IL-10) became detectable as other cytokine levels declined.
Conclusions:
- High-dose cytarabine treatment induces a sequential release of proinflammatory cytokines, starting with TNF-α.
- These cytokines are likely mediators of the symptoms associated with the cytarabine syndrome.
- Understanding this cytokine cascade may inform strategies to manage treatment-related toxicities.
Background:
Treatment with high-dose cytarabine (1-beta-D-arabinofuranosylcytosine) is often associated with an acute febrile reaction sometimes including abdominal pain, myalgia, and rash. The similarity of these symptoms to those caused by hypersecretion of cytokines in the systemic inflammatory response syndrome (SIRS) prompted us to investigate the plasma levels of proinflammatory cytokines during treatment of children with high-dose cytarabine.
Procedure:
Sixteen children treated for hematological malignancies and in clinical remission were studied during treatment with six infusions of cytarabine given every 12 hr at a dose of 2 g/m(2). Blood samples for analysis of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1gamma (IL-1gamma), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1ra) were obtained prior to treatment and subsequently at 12, 36 and 60 hr. Additional samples were collected as soon as fever occurred.
Results:
Thirteen of 16 patients developed fever at a median time of 30 hr following start of treatment. At 12 hr levels of TNF-alpha were elevated followed by a rise in IL-6, IFN-alpha, and IL-1ra, peaking at the onset of fever. Thereafter these levels slowly declined whereas low IL-10 levels became detectable.
Conclusions:
We conclude that high-dose cytarabine treatment often induces release of TNF-alpha followed by the sequential release of other proinflammatory cytokines. Most likely these cytokines mediate the development of symptoms comprising the cytarabine syndrome.