Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and septic shock. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Infectious Diseases Année : 2010

Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and septic shock.

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-00744207 , version 1 (22-10-2012)

Identifiants

Citer

Pierre Tattevin, Delphine Monnier, Olivier Tribut, Joelle Dulong, Nadège Bescher, et al.. Enhanced indoleamine 2,3-dioxygenase activity in patients with severe sepsis and septic shock.. Journal of Infectious Diseases, 2010, 201 (6), pp.956-66. ⟨10.1086/650996⟩. ⟨hal-00744207⟩
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