Blockade of Indoleamine 2,3-Dioxygenase Protects Mice against Lipopolysaccharide-Induced Endotoxin Shock
- Authors
- Jung, In Duk; Lee, Min-Goo; Chang, Jeong Hyun; Lee, Jun Sik; Jeong, Young-Il; Lee, Chang-Min; Park, Won Sun; Han, An; Seo, Su-Kil; Lee, Sang Yong; Park, Yeong-Min
- Issue Date
- 1-3월-2009
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Citation
- JOURNAL OF IMMUNOLOGY, v.182, no.5, pp.3146 - 3154
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Volume
- 182
- Number
- 5
- Start Page
- 3146
- End Page
- 3154
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/120450
- DOI
- 10.4049/jimmunol.0803104
- ISSN
- 0022-1767
- Abstract
- Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO-/-) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO-/-. or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment. The Journal of Immunology, 2009, 182: 3146-3154.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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