Tryptophan Consumption Research Articles

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration. A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events. This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.

Sleep Patterns and Tryptophan Consumption among Students at Spanish Universities: The Unihcos Project.

The objective of this cross-sectional study was to explore sleep patterns and the potential relationship between sleep and tryptophan intake among Spanish university students. A total of 11,485 students self-reported their sleep and dietary patterns and habits. Tryptophan intake was calculated using a food intake matrix and results were presented as quartiles of total intake. Short sleep duration prevalence was 51.0%, with males exhibiting a significantly higher frequency. A total of 55.0% of participants presented inadequate sleep efficiency, with males again presenting a higher rate. Median tryptophan intake was 692.16 ± 246.61 mg/day, 731.84 ± 246.86 mg/day in males and 677.24 ± 244.87 mg/day in females (p = 0.001). Dietary tryptophan intake below the first quartile (<526.43 mg/day) was associated with a higher risk of short sleep duration in males (1.26; 95%CI: 1.02-1.55) and females (1.19; 95%CI: 1.05-1.34) and with the Athens Insomnia Scale insomnia in males (2.56; 95%CI: 1.36-4.82) and females (1.47; 95%CI: 1.10-2.05). Regarding academic specializations, females in the humanities field showed a higher risk of Athens Insomnia Scale insomnia due to low tryptophan intake (Q1: 3.15; 95% CI: 1.04-9.55 and Q2: 3.41; 95%CI: 1.01-11.5). In summary, lower tryptophan consumption appears to be associated with poorer sleep quality in Spanish university students; however, other social factors affecting students may also influence sleep quality. These findings have important implications for nutritional recommendations aimed at enhancing tryptophan intake to improve sleep quality.

Surface-Enhanced Raman Scattering Monitoring of Tryptophan Dynamics in 3D Pancreatic Tumor Models.

In the intricate landscape of the tumor microenvironment, both cancer and stromal cells undergo rapid metabolic adaptations to support their growth. Given the relevant role of the metabolic secretome in fueling tumor progression, its unique metabolic characteristics have gained prominence as potential biomarkers and therapeutic targets. As a result, rapid and accurate tools have been developed to track metabolic changes in the tumor microenvironment with high sensitivity and resolution. Surface-enhanced Raman scattering (SERS) is a highly sensitive analytical technique and has been proven efficient toward the detection of metabolites in biological media. However, profiling secreted metabolites in complex cellular environments such as those in tumor-stroma 3D in vitro models remains challenging. To address this limitation, we employed a SERS-based strategy to investigate the metabolic secretome of pancreatic tumor models within 3D cultures. We aimed to monitor the immunosuppressive potential of stratified pancreatic cancer-stroma spheroids as compared to 3D cultures of either pancreatic cancer cells or cancer-associated fibroblasts, focusing on the metabolic conversion of tryptophan into kynurenine by the IDO-1 enzyme. We additionally sought to elucidate the dynamics of tryptophan consumption in correlation with the size, temporal evolution, and composition of the spheroids, as well as assessing the effects of different drugs targeting the IDO-1 machinery. As a result, we confirm that SERS can be a valuable tool toward the optimization of cancer spheroids, in connection with their tryptophan metabolizing capacity, potentially allowing high-throughput spheroid analysis.

Circular RNAs Mediate the Effects of Dietary Tryptophan on the Transformation of Muscle Fiber Types in Weaned Piglets.

The nutritional composition of the diet significantly impacts the overall growth and development of weaned piglets. The current study aimed to explore the effects and underlying mechanisms of dietary tryptophan consumption on muscle fiber type transformation during the weaning period. Thirty weaned piglets with an average body weight of 6.12 ± 0.16 kg were randomly divided into control (CON, 0.14% Trp diet) and high Trp (HT, 0.35% Trp) groups and maintained on the respective diet for 28 days. The HT group of weaned piglets exhibited highly significant improvements in growth performance and an increased proportion of fast muscle fibers. Transcriptome sequencing revealed the potential contribution of differentially expressed circular RNAs toward the transformation of myofiber types in piglets and toward the regulation of expression of related genes by targeting the microRNAs, miR-34c and miR-182, to further regulate myofiber transformation. In addition, 145 DE circRNAs were identified as potentially protein-encoding, with the encoded proteins associated with a myofiber type transformation. In conclusion, the current study greatly advances and refines our current understanding of the regulatory networks associated with piglet muscle development and myofiber type transformation and also contributes to the optimization of piglet diet formulation.

Association between consumption of tryptophan with sleep quality in King Saud University students

This study aimed to evaluate the relationship between sleep quality and tryptophan consumption in King Saud University students by using a PSQI questionnaire. This study was conducted during the COVID-19 pandemic, and it included 122 Saudi students, who received the PSQI questionnaire via Twitter, Telegram, and WhatsApp. All data was encoded in Excel for statistical analysis. Generally, low consumption levels were noted for tryptophan, coffee/tea, and soft and energy drinks in 42.6 %, 47.5 %, and 76.2 % of the participants, respectively, whereas dairy consumption was high in 32 % of the participants. Moderate consumption of caffeinated drinks was noted in 50.8 % of the participants. Meanwhile, moderate scores were noted for sleep quality, sleep duration, sleep delay, and fatigue during day time; high scores for inability to sleep within 20 mins after going to bed were noted in only 25.4 % of the participants. When the obtained data was examined in three groups, gender (p = 0.02), specialization (p = 0.02), not falling asleep within 20 min (p = 0.003), sleep delay (p = 0.01), feeling cold during sleep (p = 0.02), and having a good sleep in the previous month (p = 0.04) were associated. By contrast, no association was observed between tryptophan consumption and sleep quality. Interventional studies involving a large sample size, gender bias, other age groups, and other ethnic populations should be carried out in the future.

The Relationship of Depression and Stress with Tryptophan Consumption among University Youth

The Relationship of Depression and Stress with Tryptophan Consumption among University Youth

Tryptophan regulates Drosophila zinc stores

Zinc deficiency is commonly attributed to inadequate absorption of the metal. Instead, we show that body zinc stores in Drosophila melanogaster depend on tryptophan consumption. Hence, a dietary amino acid regulates zinc status of the whole insect—a finding consistent with the widespread requirement of zinc as a protein cofactor. Specifically, the tryptophan metabolite kynurenine is released from insect fat bodies and induces the formation of zinc storage granules in Malpighian tubules, where 3-hydroxykynurenine and xanthurenic acid act as endogenous zinc chelators. Kynurenine functions as a peripheral zinc-regulating hormone and is converted into a 3-hydroxykynurenine–zinc–chloride complex, precipitating within the storage granules. Thus, zinc and the kynurenine pathway—well-known modulators of immunity, blood pressure, aging, and neurodegeneration—are physiologically connected.

A192 CONSUMPTION OF FOOD LOWER IN TRYPTOPHAN IS ASSOCIATED WITH SIGNIFICANT ANXIETY IN PATIENTS WITH CELIAC DISEASE

BackgroundTryptophan, an essential amino acid found in many protein-based foods, has been involved in the pathogenesis of mood disorders and celiac disease (CeD). However, dietary tryptophan consumption has not been investigated in CeD.AimsTo estimate 1) differences in tryptophan content in food consumed in CeD patients compared to matched healthy controls (HC), and 2) whether consumption of tryptophan is associated with the presence of anxiety and depression in patients with CeD.MethodsThis prospective observational study examined adult patients with a diagnosis of CeD, based on positive specific serology and confirmed by duodenal biopsies, enrolled in the Celiac Registry at McMaster University. A group of sex matched HC were recruited from within the community. Participants completed several questionnaires to evaluate, gastrointestinal symptoms (GSRS), Anxiety and Depression (HADS), and dietary intake of tryptophan (Modified Food Frequency Questionnaire). In addition, CeD patients were assessed for celiac disease activity (CSI), gluten-free diet (GFD) adherence (CDAT) and nutritional status. HADs >11 denoted significant anxiety or depression. Cut-off for low vs high amount of tryptophan content in food was established based on the median tryptophan food content in the HC population.ResultsA total of 443 participants were enrolled in the study; 222 with CeD and 221 controls. The majority of participants were female (74.3%) and the adherence to the GFD was very good (Median CDAT=13; IQR 11–15). The CeD patients were older than HC (Median age, yrs. CD= 40 vs HC= 35; p<0.01). Patients with CeD consumed higher amount of tryptophan compared with HC (Median tryptophan g/day CeD=4.41 vs HC=3.31; p<0.01). There were 157 active CeD patients (CSI ≧ 30). There was no difference in tryptophan consumption between patients with and without active CeD (OR=1.021; 95%CI 0.86–1.21; p=0.88). There was no association between tryptophan consumption and gastrointestinal symptoms or depression scores. Fifteen % of the overall population and 18% of the CeD population had anxiety. There was an increased risk of anxiety in the overall population that consumed low amount of tryptophan (OR=1.87; 95%CI 1.01–3.11; p=0.04), and the risk was greater in the CeD population (OR=4.57; 95%CI 1.26–16.41; p<0.01).ConclusionsConsumption of food with lower amounts of tryptophan in patients with CeD is associated with significant anxiety, which may influence disease management. Future studies should evaluate whether increasing tryptophan in the diet compared to supplements improves outcomes in CeD population, especially in those with anxiety.Funding AgenciesNone

Dietary tryptophan and the risk of obesity and type 2 diabetes: Total effect and mediation effect of sleep duration.

The aims of this study were to examine the effects of tryptophan consumption on obesity and type 2 diabetes (T2D) risk and whether sleep duration mediates these effects. Overall, data of 7,908 participants were obtained from the China Health and Nutrition Survey (1997-2011). A total of 6,373 and 4,398 participants who reported sleep duration and had blood samples, respectively, were incorporated into subgroup analyses. Multivariate Cox regression models were used to assess the associations between tertiles of tryptophan intake with obesity and T2D. General linear regression models were used to evaluate the effect of tryptophan on sleep time and plasma biomarkers. Dietary tryptophan was significantly associated with decreased risk of obesity and T2D risk (hazard ratio tertile 3 to tertile 1 : 0.602 [95% CI: 0.500-0.724]; 0.693 [95% CI: 0.565-0.850]). Sleep duration was significantly higher, and hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-100 (APO-B) were lower in the high tertile of tryptophan compared with the low tertile (p < 0.05). In addition, mediation effects on the associations of tryptophan intake with obesity and T2D risk were observed for sleep duration (estimated mediation percentage: 31.902% and 37.391%). Dietary tryptophan showed advantageous effects on obesity and T2D risk. Furthermore, sleep duration potentially mediated for these effects.

Dietary Tryptophan and the Risk of Metabolic Syndrome: Total Effect and Mediation Effect of Sleep Duration.

PurposeTryptophan affects energy homeostasis, glucose metabolism, blood pressure, and sleep. However, studies investigating the association between tryptophan and metabolic syndrome (MetSyn) are rare. We aimed to investigate the associations of dietary tryptophan with MetSyn incidence and potential mediation via sleep duration.MethodsData of 7890 participants were obtained from the China Health and Nutrition Survey (1997–2011) (male: 49.9%; mean age=43.43 years;median follow-up=129.76 months; MetSyn incidence: 16.3%). A combination of individual 24-hour recall and household survey was used to assess dietary intake. In total, 6720 and 4474 participants who reported sleep duration and had blood samples taken, respectively, were incorporated into subgroup analyses. MetSyn was defined according to National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III criteria (2004), and tryptophan consumption and sleep duration were assessed by self-report in each survey. Multivariate Cox regression models were used to assess the associations between tertiles of tryptophan intake and MetSyn. Generalized linear regression models were used to evaluate the effect of tryptophan on sleep duration and plasma biomarkers.ResultsDietary tryptophan showed a protective effect on the risk of MetSyn. The hazard ratio (95% CI) of MetSyn was 0.77 (0.65–0.90) for individuals with a high tertile of tryptophan. Sleep duration was significantly higher, and HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APO-B) were lower in the high tertile of tryptophan compared to the low tertile (P<0.05). In addition, mediation effects on the association between tryptophan intake and MetSyn risk were observed for sleep duration (estimated mediation percentage: 26.5%).ConclusionOur study demonstrated a negative association between dietary tryptophan and MetSyn incidence, and the mediation effect of sleep duration on this association, after adjusting for numerous confounders such as nutrients and food patterns. These findings may have important public health implications for the improvement of cardiometabolic health.

A novel prodrug and its nanoformulation suppress cancer stem cells by inducing immunogenic cell death and inhibiting indoleamine 2, 3-dioxygenase

Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT–SS–NLG919 (CN) and its nanoformulation CN@PLA-HES-FA (CN@PHF), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and CN@PHF promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-β, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation CN@PHF are promising candidates for the treatment of intractable TNBC.

Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

RELATIONSHIP BETWEEN GENDER, TRYPTOPHAN AND VITAMIN B3 CONSUMPTION PATTERNS WITH EMOTIONAL EATING IN OVERWEIGHT ADOLESCENTS

Emotional eating is the propensity to eat in response of negative emotions such as stress, anxiety and depression. Adolescents with overweight may experience an increase in leptin levels as well as disruption of serotonin resulting in disruption of sensitivity in regulating appetite and emotions, thereby causing emotional eating. Emotional eating can be aff ected by several factors including gender and fulfi llment of nutrients such as tryptophan and vitamin B3 as substances that help the production of serotonin in the body. This study aimed to examine the relationship between gender, tryptophan and vitamin B3 consumption patterns with emotional eating in overweight adolescents. This was cross sectional study in adolescents ranges 15–18 years with overweight or obesity status in Surakarta. In total 122 adolescents taken by purposive sampling method. Emotional eating data were obtained from the Eating and Appraisal Due to Emotions and Stress (EADES) questionnaire while the consumption patterns data were obtained using Food Frequency Questionnaire (FFQ). This study that there was a relationship between tryptophan consumption pattern with emotional eating in overweight adolescents, but there was no relationship between gender and vitamin B3 consumption pattern with emotional eating in overweight adolescents. It can be concluded that there was a relationship between Tryptophan consumption pattern with emotional eating in overweight adolescents and there was no relationship between gender and vitamin B3 consumption pattern with emotional eating in overweight adolescents.

Cell-free DNA promotes malignant transformation in non-tumor cells

Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.

Dietary tryptophan and bone health: a cross-sectional, population-based study.

Tryptophan metabolites, such as serotonin, influence bone. We sought to determine the relationship between dietary intake of tryptophan and bone health in a population-based study of men and women. Participants (1033 women and 900 men, aged 20-98years) enrolled in the Geelong Osteoporosis Study (GOS) were investigated. Dietary information was collected using a validated questionnaire. Tryptophan levels were calculated (mg/day) in accordance with Food Standards Australia and New Zealand and dichotomised according to the median. Bone mineral density (BMD; g/cm2) was measured at the spine (postero-anterior projection) and total hip using dual-energy X-ray absorptiometry. Stiffness index (SI), broadband ultrasound attenuation (BUA) and speed of sound (SOS) were derived from quantitative heel ultrasound. Linear regression models were used to test associations between dietary tryptophan and bone health, after adjustment for potential confounders. Tryptophan intakes ranged from 112 to 3796mg/day (median 1035) in men and 115-2869mg/day (median 885) in women. In men older than 45years and women, a high tryptophan intake was associated with greater hip BMD compared to participants with a low tryptophan intake (p = 0.002 and p = 0.04, respectively); however, these relationships were attenuated by age (all p > 0.05). Participants with high tryptophan intake had greater BUA and SI compared to participants with low tryptophan intake (men; BUA, p = 0.02 and SI, p = 0.02, and women; BUA, p = 0.03 and SI, p = 0.08), yet also attenuated by age (all p > 0.05). No association was found between tryptophan intake and bone health in this population, which suggests a non-critical role of superfluous tryptophan consumption on the skeleton.

Effects of Diet on Sleep: A Narrative Review.

Many processes are involved in sleep regulation, including the ingestion of nutrients, suggesting a link between diet and sleep. Aside from studies investigating the effects of tryptophan, previous research on sleep and diet has primarily focused on the effects of sleep deprivation or sleep restriction on diet. Furthermore, previous reviews have included subjects with clinically diagnosed sleep-related disorders. The current narrative review aimed to clarify findings on sleep-promoting foods and outline the effects of diet on sleep in otherwise healthy adults. A search was undertaken in August 2019 from the Cochrane, MEDLINE (PubMed), and CINAHL databases using the population, intervention, control, outcome (PICO) method. Eligible studies were classified based on emerging themes and reviewed using narrative synthesis. Four themes emerged: tryptophan consumption and tryptophan depletion, dietary supplements, food items, and macronutrients. High carbohydrate diets, and foods containing tryptophan, melatonin, and phytonutrients (e.g., cherries), were linked to improved sleep outcomes. The authors posit that these effects may be due in part to dietary influences on serotonin and melatonin activity.

61 Nutritive feed ingredients that pose toxicological potential

Abstract A variety of different substances can promote adverse effects on livestock and companion animals, varying from a decrease in overall growth, to frank toxicological response and death. Many substances that are the cause of adverse effects are either components in feed, part of the forage landscape for grazing animals, or even a part of the nutritive feed composition for pets. It has been well-known that vitamin D intake increases bone mineralization, but methionine consumption may also positively impact bone density. Excess consumption of other nutrients may lead to adverse effects, as current research found that excess tryptophan consumption in weaned pigs adversely affects intestinal morphology and tight junction proteins in other species. However, some studies have found that different animals can have opposing effects from consuming the same substances. For example, a study in mice has found that consumption of chitosan impairs intestinal barrier integrity, while twice the intake by weaned piglets improved the average daily gain. This presentation will discuss examples of nutrients and other substances that may adversely impact the growth and reproductive capacity of companion animals and livestock, underscoring the need for the completion of safety studies of potentially new ingredients to evaluate their long-term use in commercial feed formulations.

The effects of a sleep/recovery supplement: 'Night Time Recharge' on sleep parameters in young adults.

Concentrated cherry juice reportedly contains melatonin which, in turn, has been highlighted as an important regulator in initiating sleep. The present investigation aims to clarify whether Night Time Recharge (NTR), a marketed sleep aid containing cherry extract, improves key sleep parameters in young, active adults with mildly poor sleep. A double-blind, randomized, placebo-controlled, cross-over study design was employed. Twenty participants (nine female) consumed either NTR or a placebo for seven days. Accelerometers were used to assess sleep quality and physical activity levels. Urinary levels of 6-sulphatoxymelatonin (6-SMT), a marker of melatonin synthesis, was assessed via enzyme-linked immunosorbent assay. 6-SMT levels increased following NTR treatment (28.95 ng/ml) compared with placebo (4.0 ng/ml) (p < 0.001). There was also a significant difference (p = 0.047) in dietary tryptophan consumption during the NTR treatment (1236 mg) versus placebo (1149 mg). No trace of melatonin was detected from our analysis of the supplement. NTR had no significant effect on any sleep parameters with the exception of sleep latency (p = 0.001). As chemical analysis of NTR by liquid-chromatography mass-spectrometry identified no detectable melatonin, the tryptophan content of the supplement is a likely reason for improvement in sleep latency. These results are in contrast to previous studies which have found a positive effect on sleep following cherry supplementation. Future work should focus on sleep latency and investigating whether cherry juice is effective in participants with problems in initiating sleep.

Bystander inhibition of humoral immune responses by Epstein-Barr virus LMP1.

Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent individuals, suggesting that it may contribute to persistent EBV infection. In this study, we generated and analyzed mice that expressed LMP1 under the control of the CD19 or activation-induced cytidine deaminase (AID) promoter. Expression of LMP1 induced activation of B cells but severely inhibited their differentiation into antibody-secreting cells (ASCs) in vitro and GC B cells in vivo. LMP1-expressing (LMP1+) B cells not only suppressed the functions of wild-type (WT) B cells in in vitro co-culture, but also blocked differentiation of WT B cells into GC B cells and ASCs in immunized bone marrow chimeric mice. Microarray analysis revealed that the gene encoding indoleamine 2,3-dioxygenase 1 (IDO1), a major enzyme involved in the tryptophan metabolic process, was highly induced by LMP1. Either inhibition of IDO1 activity by methyl-l-tryptophan or knockout of Ido1 in LMP1+ B cells could rescue WT B cells from such suppression. IDO1-induced tryptophan consumption and production of tryptophan metabolites appeared to be responsible for inhibition of B-cell function. We conclude that LMP1 expression in antigen-committed B cells not only directly impairs GC B-cell differentiation, but also indirectly inhibits the functions of neighboring B cells, resulting in suppression of humoral immune responses. Such bystander inhibition by LMP1+ B cells may contribute to immune evasion by EBV.

Serum neopterin concentrations and tryptophan degradation pattern in patients with late stage larynx carcinoma

AbstractAs the disease-free 5-year-survival of late stage laryngeal carcinoma patients is extremely low, indoleamine-2,3-dioxygenase-1 (IDO)-induced tryptophan degradation may represent an immune escape mechanism which plays an important role in cancer spreading in advanced stage laryngeal cancers. We examined whether the late stage laryngeal cancer enhances tumor immune evasion by the expression of systemic IDO activities and chronic cellular immune activation. Twenty-two of 42 male laryngeal cancer patients were classified as late stage cancer according to American Joint Committee on Cancer (AJCC) criteria. Their serum neopterin, tryptophan and kynurenine concentrations were compared with 30 cancer-free individuals. IDO activity was approved by correlation between serum neopterin and kynurenine/tryptophan. Late stage cancer patients preoperatively showed a significantly higher IDO activity compared to controls and early stage cancer cases. Six months after tumor removal, late stage cancer patients although having higher serum neopterin concentration compared to early stage patients or controls, they showed a significant decrease in IDO activity and tryptophan consumption. Increased systemic IDO activity may provoke the escape of tumor cells from the immune surveillance of the host. High IDO activity is due to the presence of tumor mass. Persistence of high serum neopterin levels despite tumor removal may indicate poor prognosis.