The new normal: Immunomodulatory agents against sepsis immune suppression

Noelle A. Hutchins, Jacqueline Unsinger, Richard S. Hotchkiss, Alfred Ayala

Research output: Contribution to journalReview articlepeer-review

192 Scopus citations


Sepsis is the leading cause of death among critically ill patients in intensive care units, and treatment options are limited. Therapies developed against the proinflammatory stage have failed clinically; therefore, new approaches that target the host immune response in sepsis are necessary. Increasing evidence suggests that a major pathophysiological event in sepsis is immune suppression, often resulting in secondary fungal, bacterial, or viral infections. Recent studies from animal sepsis models and patient samples suggest that cytokines such as interleukin-7 (IL-7), IL-15, granulocyte macrophage colony-stimulating factor (GM-CSF), as well as co-inhibitory molecule blockade, such as anti-programmed cell death receptor-1 (anti-PD-1) and anti-B and T lymphocyte attenuator (anti-BTLA), may have utility in alleviating the clinical morbidity associated with sustained sepsis. This review discusses some of these novel immunomodulatory agents and evaluates their potential use as therapeutics.

Original languageEnglish
Pages (from-to)224-233
Number of pages10
JournalTrends in Molecular Medicine
Issue number4
StatePublished - Apr 2014


  • Co-inhibitory molecules
  • Cytokines
  • Immunomodulatory agents
  • Immunosuppression
  • Sepsis


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