Prolonged Reactive Oxygen Species Production following Septic Insult

Isaac J. Jensen, Patrick W. McGonagill, Roger R. Berton, Brett A. Wagner, Elvia E. Silva, Garry R. Buettner, Thomas S. Griffith, Vladimir P. Badovinac

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The dysregulated host response and organ damage following systemic infection that characterizes a septic event predisposes individuals to a chronic immunoparalysis state associated with severe transient lymphopenia and diminished lymphocyte function, thereby reducing long-term patient survival and quality of life. Recently, we observed lasting production of reactive oxygen species (ROS) in mice that survive sepsis. ROS production is a potent mechanism for targeting infection, but excessive ROS production can prove maladaptive by causing organ damage, impairing lymphocyte function, and promoting inflammaging, concepts paralleling sepsis-induced immunoparalysis. Notably, we observed an increased frequency of ROS-producing immature monocytes in septic hosts that was sustained for greater than 100 days postsurgery. Recent clinical trials have explored the use of vitamin C, a potent antioxidant, for treating septic patients. We observed that therapeutic vitamin C administration for sepsis limited ROS production by monocytes and reduced disease severity. Importantly, we also observed increased ROS production by immature monocytes in septic patients both at admission and ∼28 days later, suggesting a durable and conserved feature that may influence the host immune response. Thus, lasting ROS production by immature monocytes is present in septic patients, and early intervention strategies to reduce it may improve host outcomes, potentially reducing sepsis-induced immunoparalysis.

Original languageEnglish (US)
Pages (from-to)477-488
Number of pages12
Issue number6
StatePublished - Jun 1 2021

Bibliographical note

Funding Information:
Received for publication March 12, 2021. Accepted for publication May 20, 2021. Address correspondence and reprint requests to: Vladimir P. Badovinac, University of Iowa, 1023 Medical Laboratories, 25 Grand Avenue, Iowa City, IA. 52242. E-mail address: ORCIDs: 0000-0002-3107-3961 (I.J.J.); 0000-0003-1517-8541 (R.R.B.); 0000-0002-0094-7259 (B.A.W.); 0000-0002-2733-1999 (E.E.S.); 0000-0002-5594-1903 (G.R.B.); 0000-0002-7205-9859 (T.S.G.); 0000-0003-3180-2439 (V.P.B.). This work was supported by National Institutes of Health Grants AI114543 (to V.P.B.), GM134880 (to V.P.B.), GM115462 (to T.S.G.), GM140881 (to T.S.G.), CA217797 (to G.R.B.), T32AI007511 (to I.J.J.), and T32AI007485 (to I.J.J. and R.R.B.) and Veterans Health Administration Merit Review Award I01BX001324 (to T.S.G.) Abbreviations used in this article: AT, adoptive transfer; CLP, cecal ligation and puncture; LCMV, lymphocytic choriomeningitis virus; LCMV-Arm, LCMV-Armstrong; ROS, reactive oxygen species; SPExp, specific pathogen–experienced; SPFree, specific pathogen–free. This article is distributed under the terms of the CC BY 4.0 Unported license.

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