Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia

Suzuki, Yuzo; Suda, Takafumi; Yokomura, Koushi; Suzuki, Masako; Fujie, Manabu; Furuhashi, Kazuki; Hahimoto, Dai; Enomto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Inui, Naoki; Nakano, Yuichi; Nakamura, Hirotoshi; Chida, Kingo

doi:10.1016/j.jinf.2011.07.003

Cited by 33 publications

(38 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Only a few studies have investigated the impact of the TRP/5-HT metabolism in patients with CAP. Similarly to our study, Suzuki et al [11] found an increase in IDO according to severity in a smaller cohort of CAP patients (129 subjects). Also, they studied short-term outcome and did multivariate regression analysis with laboratory parameters (e.g.…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier

Ottiger

Vögeli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

Background: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP). Methods: We measured tryptophan, serotonin and kynurenine on admission plasma samples from CAP patients included in a previous multicenter trial by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We studied their association with inflammation (C-reactive protein), infection (procalcitonin) and clinical outcome. Results: Mortality in the 268 included patients was 45% within 6 years of follow-up. IDO and kynurenine showed a

show abstract

Section: Discussionsupporting

confidence: 90%

“…Serum activity of IDO predicted shortterm prognosis in a small cohort of 129 CAP patients [11]. However, this study did not measure serotonin.…”

Section: Introductionmentioning

confidence: 86%

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Meier

Ottiger

Vögeli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

show abstract

“…To date, several studies have shown that an increase in IDO activity is associated with poor prognosis in cancer patients, suggesting that IDO activity can be used as a prognostic factor (4, 7, 23). However, there have been no studies to measure serum IDO activity in TB patients and to determine its prognostic significance.Recently, we developed a method for assessing IDO activity in human serum using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS-MS) (15,16). This method enables the simultaneous measurement of Kyn and Trp in human serum.…”

mentioning

confidence: 99%

“…Recently, we developed a method for assessing IDO activity in human serum using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS-MS) (15,16). This method enables the simultaneous measurement of Kyn and Trp in human serum.…”

mentioning

confidence: 99%

Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis

Suzuki

Suda

Asada

et al. 2012

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

d Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P < 0.0001, P < 0.0001, and P < 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.T uberculosis (TB) remains a worldwide health problem, with 8.8 million new cases per year (21, 24). Advanced diagnosis technique, such as PCR for TB DNA and gamma interferon (IFN-␥) release assays (IGRAs), have improved detection of TB, and progress in multidrug combination therapy and expansion of directly observed therapy (DOTS) has increased the treatment completion rate and reduced the relapse rate. However, TB still causes over 1.6 million deaths per year (21,24). To assess the disease activity, therapeutic response, or risk for relapse, a large number of candidate biomarkers, such as sputum microbiologic examinations, serum neopterin, IGRAs, and urine tuberculous DNA, have been vigorously investigated (18, 21). However, there are few useful markers for predicting mortality in pulmonary TB (PTB).Indoleamine 2, 3-dioxygenase (IDO) is the rate-limiting enzyme that catalyzes tryptophan (Trp) degradation along the kynurenine (Kyn) pathway (9,11,12,19,25). In infectious diseases, IDO was initially considered an antimicrobial molecule acting through local starvation of Trp, which is an essential amino acid for bacterial growth. Interestingly, recent studies have unveiled a novel immunoregulatory role of IDO. By reducing the local Trp concentration and producing immunomodulatory Trp metabolites, such as Kyn, IDO potently inhibits T-cell functions and generates regulatory T cells (Treg), leading to immune suppression or tolerance. More interestingly, this immunoregulatory role of IDO has been shown to be associated with the immune esc...

show abstract

“…Сепсис Имеющиеся литературные данные свидетель-ствуют о теснейшей зависимости клинической картины при сепсисе различного генеза и уровня активности IDO. Описано увеличение отноше-ния кинуренин/триптофан как прогностический маркер выраженности течения и смертности при community-acquired pneumonia [74]. Увеличение активности IDO также оценивается как предик-тор выраженности и смертности при сепсисе, а повышенная пропорция кинуренин/триптофан при сепсисе коррелирует с повышенным уровнем IFNγ и IL-10, которые участвуют в пролонгации индукции IDO, способствуя снижению у боль-ных количества CD4 + и CD8 + Т-клеток.…”

Section: клеточные механизмы защиты от триптофано-вого «голода»unclassified

Tryptophan and Indoleamine-2,3-Dioxygenase (Ido) in Pathogenesis of Immunosuppressive Clinical Conditions

Козлов¹,

Демина²

2017

Med. immunol.

View full text Add to dashboard Cite

Адрес для переписки:Козлов Владимир Александрович ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии» 630099, Россия, г. Новосибирск, ул. Ядринцевская, 14. Тел.: 8 (383) 222-66-27. Факс: 8 (383) 222-70-28. E-mail: vakoz40@yandex.ru Address for correspondence : Kozlov Vladimir A. Research Institute of Fundamental and Clinical Immunology 630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., Образец цитирования: иммунология, 2017. Т. 19, № 3. С. 225-240. doi: 10.15789/1563-0625-2017-3-225-240 © Козлов В.А., Демина Д.В., 2017 For citation: V. A. Kozlov, Immunologiya, 2017, Vol. 19, no. 3, pp. 225-240. doi: 10.15789/1563-0625-2017-3-225-240 DOI: 10.15789/1563-0625-2017 ТРИПТОФАН И INDOLEAMINE-2,3-DIOXYGENASE (IDO) В ПАТОГЕНЕЗЕ ИММУНОКОМПРОМЕТИРОВАННЫХ ЗАБОЛЕВАНИЙКозлов В.А., Демина Д.В. ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии», г. Новосибирск, РоссияРезюме. Все больше и больше литературных данных свидетельствуют о ведущей роли в форми-ровании иммуносупрессорных механизмов фермента indoleamin 2,3-deoxygenase (IDO), которая продуцируется в основном дендритными клетками, в индукции которой участвует в основном IFNγ и функции которой состоят в индукции катаболизма незаменимой аминокислоты триптофана. Уже одно снижение уровня триптофана в околоклеточной среде обуславливает подавление ряда функ-ций клеток иммунной системы и индукцию регуляторных Т-клеток. Появление ряда катаболитов триптофана еще более усугубляет иммунодепрессивное состояние, индуцированное повышенной экспрессией IDO. Предполагается, что цепочка из IDO, триптофана и его катаболитов в значитель-ной степени определяет формирование гиперсупрессорного состояния при опухолевом росте и гипо-(или недостаточного) супрессорного состояния при аутоиммунных и аллергических заболеваниях. Отсюда вытекают и новые задачи в терапии: найти способы терапии, направленные на снижение ак-тивности фермента IDO, участвующего в индукции клеток-супрессоров при опухолевом росте, и в то же время направленные на стимуляцию активности данного фермента для повышения супрессорной активности регуляторных клеток. that the interactions between IDO, tryptophan and its catabolites largely determine a development of hypersuppressor state in tumor growth and a hypo-(or lack of) suppressor status in autoimmune and allergic diseases. This implies some novel tasks for the therapy, including a treatment aimed for reduction of the IDO activity since the latter is involved in suppressor cell induction during tumor growth. Respectively, stimulation of IDO activity may augment suppressor activity of the regulatory cells. Ключевые слова: иммунопатология, иммуносупрессия, триптофан, indoleamine 2,3-dioxygenase, кинуренин TRYPTOPHAN AND INDOLEAMINE-2,3-DIOXYGENASE (IDO) IN PATHOGENESIS OF IMMUNOSUPPRESSIVE CLINICAL CONDITIONS

show abstract

Serum activity of indoleamine 2,3-dioxygenase predicts prognosis of community-acquired pneumonia

Cited by 33 publications

References 28 publications

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study

Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis

Tryptophan and Indoleamine-2,3-Dioxygenase (Ido) in Pathogenesis of Immunosuppressive Clinical Conditions

Contact Info

Product

Resources

About