Enhanced Indoleamine 2,3‐Dioxygenase Activity in Patients with Severe Sepsis and Septic Shock

Tattevin, Pierre; Monnier, Delphine; Tribut, Olivier; Dulong, Joëlle; Bescher, Nadège; Mourcin, Frédéric; Uhel, Fabrice; Tulzo, Yves Le; Tarte, Karin

doi:10.1086/650996

Cited by 72 publications

(75 citation statements)

References 47 publications

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“…In early stages of disease in cattle, significant differences in IDO gene expression were also detected. The cell type producing IDO is likely CD14 ϩ monocytic cells, as was found in previous studies of human PBMCs (11,46). The profile of IDO gene expression in peripheral blood cells of uninfected animals that were exposed but had no evidence of infection at the time of necropsy was markedly different from that of the infected group, with an early peak in IDO expression that returned to baseline.…”

Section: Discussionsupporting

confidence: 67%

Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

et al. 2011

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Virulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases. Mycobacterium avium subsp. paratuberculosis is an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased in M. avium subsp. paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells of M. avium subsp. paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses to M. avium subsp. paratuberculosis and other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.

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Section: Discussionsupporting

confidence: 67%

Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

et al. 2011

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“…Kynurenine on the other hand has been demonstrated to be a very potent vasodilator, which may trigger the development of hypotension during shock (26). Thus, IDO activity possibly influences the outcome of patients with trauma or septicaemia-as shown recently in several studies (13,(27)(28)(29), although tryptophan catabolism did not differ between survivors and non-survivors in our population.…”

Section: Discussionsupporting

confidence: 67%

Altered Immune Responses during Septicaemia in Patients Suffering from Haematological Malignancies

Kurz

Garimorth

Joannidis³

et al. 2012

Int J Immunopathol Pharmacol

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Septicaemia is a frequent complication in patients with haematological malignancies. In this study we analysed markers of inflammation/immune activation (C- reactive protein, interleukin-6, neopterin), tryptophan metabolites and mannose binding lectin (MBL) levels consecutively in 36 septic patients with haematological malignancies (HM) and “non-haematological” diseases [intensive care unit (ICU) patients]. During septicaemia different chronological sequences for inflammation markers CRP, IL-6 and neopterin were seen in HM and ICU patients. Septic ICU-patients presented with significantly increased tryptophan degradation and higher neopterin and CRP levels at baseline, while MBL levels were lower in this group compared to subjects with HM. Concentrations of inflammation markers Were linked to each other and associated with enhanced tryptophan degradation. Patients who died during follow-up of 28 days tended to have lower baseline MBL concentrations than survivors. Septic patients with HM showed an impaired pro-inflammatory immune response compared to patients with non-haematological diseases.

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“…Acetylcholine, the principal neurotransmitter of the vagus nerve, inhibits the production of proinflammatory cytokines from endotoxin-stimulated macrophages through the α7nAChR [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Sun

Zhang

et al. 2012

Acta Pharmacol Sin

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Aim: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. Methods: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 μg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1β were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in α7 nicotinic acetylcholine receptor (α7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. Results: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The antishock effect of combined anisodamine and neostigmine was abolished in α7 nAChR knockout mice. On the other hand, intravenous injection of the combined anisodamine and neostigmine, or the selective α7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. Conclusion:The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of α7 nAChRs.

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Enhanced Indoleamine 2,3‐Dioxygenase Activity in Patients with Severe Sepsis and Septic Shock

Abstract: 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.

Cited by 72 publications

References 47 publications

Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

Altered Immune Responses during Septicaemia in Patients Suffering from Haematological Malignancies

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

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