Inducible nitric oxide synthase contributes to immune dysfunction following Trauma

Sophie S. Darwiche*, Roman Pfeifer, Christoph Menzel, Xiangcai Ruan, Marcus Hoffman, Changchun Cai, R. Savanh Chanthaphavong, Patricia Loughran, Bruce R. Pitt, Rosemary Hoffman, Hans Christoph Pape, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Trauma results in a persistent depression in adaptive immunity, which contributes to patient morbidity and mortality. This state of immune paralysis following trauma is characterized by a change in cell-mediated immunity, specifically a depression in T-cell function and a shift toward TH2 T-cell phenotype. Upregulation of inducible nitric oxide synthase (iNOS) is well recognized after injury and contributes to the inflammatory response and organ damage early after trauma. However, it is unknown whether iNOS plays a role in adaptive immune dysfunction after trauma. This study utilized a murine model of severe peripheral tissue injury to show that iNOS is rapidly upregulated in macrophages and a (Gr-1-CD11bhi) myeloid-derived suppressor cell subpopulation in the spleen. Through the use of iNOS knockout mice, a specific iNOS inhibitor, and a nitric oxide (NO) scavenger, this study demonstrates that iNOS-derived NO is required for the depression in T-lymphocyte proliferation, interferon γ, and interleukin 2 production within the spleen at 48 h after trauma. These findings support the hypothesis that iNOS regulates immune suppression following trauma and suggest that targeting the sustained production of NO by iNOS may attenuate posttraumatic immune depression.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
Issue number5
StatePublished - Nov 2012
Externally publishedYes


  • Injury
  • MDSCs
  • T lymphocyte
  • iNOS
  • immunosuppression


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