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Stratification to predict the response to antioxidant.

Cristiane Ritter1, Larissa Constantino1, Monique Michels1

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Stratifying sepsis patients by high interleukin-6 levels identified those who benefit from antioxidant therapy, improving survival in animal models and reducing acute kidney injury in humans.

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Area of Science:

  • Biomedical Science
  • Pharmacology
  • Critical Care Medicine

Background:

  • Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
  • Antioxidant therapies have shown promise but lack targeted application in sepsis.
  • Interleukin-6 (IL-6) is a key inflammatory marker in sepsis.

Purpose of the Study:

  • To evaluate the efficacy of stratifying patients for antioxidant therapy in lethal sepsis models and hypotensive patients.
  • To determine if targeting therapy based on IL-6 levels improves outcomes.

Main Methods:

  • Rats with sepsis (cecal ligation and puncture) were stratified by plasma IL-6 levels.
  • Animals and hypotensive patients received N-acetylcysteine plus deferoxamine or placebo/saline.
  • Outcomes measured included survival, IL-6 levels, and acute kidney injury.

Main Results:

  • Antioxidant treatment improved survival in rats when given 3 and 12 hours post-sepsis induction.
  • Survival benefit was observed only in rats with high IL-6 levels.
  • In patients, high IL-6 subgroup showed reduced acute kidney injury incidence compared to low IL-6 subgroup.

Conclusions:

  • Stratification by high IL-6 levels identifies a patient population responsive to antioxidant therapy.
  • Targeting antioxidant treatment to a high inflammatory phenotype is a viable strategy.
  • This approach may optimize therapeutic efficacy in sepsis and related conditions.