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Proinflammatory cytokines mediate the systemic inflammatory response associated with high-dose cytarabine treatment

T Ek1, M Jarfelt, L Mellander

  • 1Department of Pediatrics, Göteborg University, Göteborg, Sweden.

Medical and Pediatric Oncology
|December 18, 2001
PubMed

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.
Abstract

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