Back to Search
Start Over
Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and septic shock
- Source :
- Journal of Infectious Diseases, Journal of Infectious Diseases, Oxford University Press (OUP), 2010, 201 (6), pp.956-66. ⟨10.1086/650996⟩, Journal of Infectious Diseases, 2010, 201 (6), pp.956-66. ⟨10.1086/650996⟩
- Publication Year :
- 2010
-
Abstract
- International audience; BACKGROUND: Severe sepsis results in a sustained deleterious immune dysregulation. Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism, plays a pivotal role in immune tolerance and is induced during various inflammatory conditions. METHODS: Plasma samples obtained from patients with septic shock (n = 38), severe sepsis (n = 35), or sepsis (n = 10) and from healthy donors (n = 26) were analyzed for IDO activity by high-performance liquid chromatography. Lymphocyte, monocyte, and regulatory T cell counts as well as monocytic human leukocyte antigen DR (HLA-DR) expression were quantified by flow cytometry. Peripheral blood mononuclear cells and purified CD14(+) and CD14(-) fractions were assayed in vitro for spontaneous and inducible IDO expression and activity. RESULTS: IDO activity gradually increased according to sepsis severity, and septic patients who died had higher IDO activity on admission than did survivors (P = .013). Monocytes were a major source of active IDO in normal peripheral blood. The percentage and absolute number of circulating CD14(+) cells were increased in septic patients, and their monocytes remained fully able to produce functional IDO after NF-kappaB-independent interferon gamma stimulation but not through NF-kappaB-dependent Toll-like receptor engagement. CONCLUSIONS: IDO activity is increased during severe sepsis and septic shock and is associated with mortality. IDO production could be used to better characterize monocyte reprogramming in sepsis.
- Subjects :
- Male
MESH: CD4 Lymphocyte Count
MESH: NF-kappa B
MESH: Flow Cytometry
T-Lymphocytes, Regulatory
Immune tolerance
0302 clinical medicine
Immunology and Allergy
Indoleamine 2,3-dioxygenase
MESH: Sepsis
Chromatography, High Pressure Liquid
MESH: Aged
0303 health sciences
MESH: Middle Aged
NF-kappa B
Middle Aged
Flow Cytometry
MESH: Case-Control Studies
Shock, Septic
3. Good health
Infectious Diseases
medicine.anatomical_structure
MESH: Young Adult
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
France
medicine.symptom
Adult
MESH: Shock, Septic
Inflammation
Biology
Peripheral blood mononuclear cell
Sepsis
03 medical and health sciences
Young Adult
MESH: Indoleamine-Pyrrole 2,3,-Dioxygenase
medicine
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
MESH: Chromatography, High Pressure Liquid
030304 developmental biology
Aged
MESH: Humans
Septic shock
Monocyte
MESH: T-Lymphocytes, Regulatory
MESH: Adult
HLA-DR Antigens
medicine.disease
MESH: HLA-DR Antigens
MESH: Male
CD4 Lymphocyte Count
MESH: France
Bacteremia
Case-Control Studies
Immunology
MESH: Female
030215 immunology
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 201
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The Journal of infectious diseases
- Accession number :
- edsair.doi.dedup.....6449b5bc8186ec47613709b80fcbfe33