Urinary Neopterin Concentrations Research Articles

Concentrations of urinary neopterin, but not suPAR, positively correlate with age in rhesus macaques

Identifying biomarkers of age-related changes in immune system functioning that can be measured non-invasively is a significant step in progressing research on immunosenescence and inflammaging in free-ranging and wild animal populations. In the present study, we aimed to investigate the suitability of two urinary compounds, neopterin and suPAR, as biomarkers of age-related changes in immune activation and inflammation in a free-ranging rhesus macaque (Macaca mulatta) population. We also investigated age-associated variation in gene transcription from blood samples to understand the underlying proximate mechanisms that drive age-related changes in urinary neopterin or suPAR. Neopterin was significantly positively correlated with age, and had a moderate within-individual repeatability, indicating it is applicable as a biomarker of age-related changes. The age-related changes in urinary neopterin are not apparently driven by an age-related increase in the primary signaler of neopterin, IFN-y, but may be driven instead by an age-related increase in both CD14+ and CD14− monocytes. suPAR was not correlated with age, and had low repeatability within-individuals, indicating that it is likely better suited to measure acute inflammation rather than chronic age-related increases in inflammation (i.e., “inflammaging”). Neopterin and suPAR had a correlation of 25%, indicating that they likely often signal different processes, which if disentangled could provide a nuanced picture of immune-system function and inflammation when measured in tandem.

Home gardens and distances to nature associated with behavior problems in alpine schoolchildren: Role of secondhand smoke exposure and biomarkers

Behavior problems in children are shaped by a complex intertwining of environmental, social, and biological factors. This study investigated whether more nature exposure was associated with less behavior problems and whether these associations were mediated by differences in secondhand smoke in the home, sleep problems, adiposity, and inflammation. We used cross-sectional data collected from 1251 schoolchildren (8-12 years old) in the Tyrol region of Austria and Italy. Information on sociodemographics, lifestyle, perinatal data, and housing conditions was obtained by questionnaire. Behavior problems in the past school year were rated by teachers using the Needleman questionnaire for classroom performance. We estimated nature exposure using a comprehensive naturalness index called "distance to nature" (D2N). This was calculated in several buffer sizes around the child's home and school. Presence of a home garden was assessed by self-report. Data on potential mediators including parental smoking in the home, child's urinary cotinine concentrations, sleep problems, body mass index, and urinary neopterin concentrations were also collected. Structural equation modeling was used to examine the multiple pathways between nature exposure and behavior problems. Children who lived in a home with a garden and those whose school was closer to nature exhibited less school behavior problems. The effect of proximity to nature from the school was directly associated with less behavior problems, and the effect of a home garden on behavior problems acted indirectly through a lower likelihood of secondhand smoke exposure. Associations were in unexpected directions between behavior problems and residential proximity to nature and depended on the outcome and context. Natural environments in school and home surroundings might be beneficial for school conduct and performance. Lower secondhand smoke exposure at home might be a pathway between home gardens and children's behavioral problems. Associations with residential proximity to nature in this study were in unexpected directions and warrant further investigation. These findings serve as a point of departure for investigating how proximal nature might activate health supportive pathways in children and simultaneously confer childhood health benefits via positive behavioral changes in their parents.

008 Systemic inflammatory response in relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is often described as an inflammatory disease of the central nervous system (CNS). However, the aberrant immune response may not be fully compartmentalised within the CNS. Here we present two strands of evidence for an active systemic inflammatory process in MS. First, we describe a case series of six individuals with relapsing-remitting MS (RRMS) and sustained raised serum inflammatory markers. All displayed persistent leucocytosis and/or raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), with no evidence of any other systemic or alternative neuro-inflammatory condition on long-term follow-up. All but one met criteria for rapidly-evolving severe (RES) RRMS. We hypothesised that these cases reflect the extreme end of a systemic inflammatory response spectrum in MS. Therefore, we sought to further investigate the systemic inflammatory response in RRMS by a more sensitive method, namely liquid chromatography-mass spectrometry to detect urinary neopterin, a molecular product of activated macrophages and a non-specific marker of systemic inflammation. A separate group of individuals with RRMS showed significantly higher concentrations of urinary neopterin compared to age- and gender- matched healthy controls.a.varatharaj@soton.ac.uk

Urinary neopterin, a new marker of the neuroinflammatory status in amyotrophic lateral sclerosis.

To comprehensively assess whether neopterin in urine could be a candidate biomarker for determining the neuroinflammatory status in ALS. We performed an observational, cross-sectional study in 81 pALS, 68 age- and sex-comparable healthy controls (HC), 14 patients affected by MS and 24 OND patients. ALS patients underwent a neurological evaluation to assess the global functional status evaluated by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and the disease progression rate. Urinary neopterin concentrations were determined by high-performance liquid chromatography method and were recorded at the time of first examination to assess their effect on disease severity and survival. Urinary neopterin was significantly higher in pALS (263.90 [198.71-474.90]) compared to MS (155.28 [131.74-190.38], p = < .001), OND patients (205.60 [158.96-299.41], p = 0.04) and HC (169.55 [134.91-226.10], p < .001). Moreover, a significant negative correlation was found between neopterin level and the severity of symptoms evaluated by ALSFRS-R total score (r = -0.46, p < .001) and its subscores (bulbar r = -0.34, p = 0.002; motor r = -0.33, p = 0.003; respiratory r = -0.53, p < .001), also adjusting for the effect of sex, site of onset, age at evaluation and time from onset to evaluation. Our finding indicates that urine neopterin is elevated in ALS, emphasizing the role of the cell-mediated inflammation in the disease. Moreover, whether confirmed in further studies, our results will underline the neopterin's potential use as non-invasive clinical biomarker of ALS, to discriminate patients possibly candidates to clinical interventions aimed to interfere the neuroinflammatory processes.

Detection of neopterin in the urine of captive and wild platyrrhines

BackgroundNon-invasive biomarkers can facilitate health assessments in wild primate populations by reducing the need for direct access to animals. Neopterin is a biomarker that is a product of the cell-mediated immune response, with high levels being indicative of poor survival expectations in some cases. The measurement of urinary neopterin concentration (UNC) has been validated as a method for monitoring cell-mediated immune system activation in multiple catarrhine species, but to date there is no study testing its utility in the urine of platyrrhine species. In this study, we collected urine samples across three platyrrhine families including small captive populations of Leontopithecus rosalia and Pithecia pithecia, and larger wild populations of Leontocebus weddelli, Saguinus imperator, Alouatta seniculus, and Plecturocebus toppini, to evaluate a commercial enzyme-linked immunosorbent assay (ELISA) for the measurement of urinary neopterin in platyrrhines.ResultsOur results revealed measured UNC fell within the sensitivity range of the assay in all urine samples collected from captive and wild platyrrhine study species via commercial ELISA, and results from several dilutions met expectations. We found significant differences in the mean UNC across all study species. Most notably, we observed higher UNC in the wild population of L. weddelli which is known to have two filarial nematode infections compared to S. imperator, which only have one.ConclusionOur study confirms that neopterin is measurable via commercial ELISA in urine collected from captive and wild individuals of six genera of platyrrhines across three different families. These findings promote the future utility of UNC as a promising biomarker for field primatologists conducting research in Latin America to non-invasively evaluate cell-mediated immune system activation from urine.

Potential utilization of neopterin measurements in the assessment of pyrexia in metastatic melanoma treated with combined targeted therapy: a case report

Abstract In patients with metastatic melanoma the advent of targeted therapy and immune checkpoint inhibitors has transformed the management of advanced and metastatic disease, resulting in improved outcomes. Neopterin is a biomarker of immune activation increased in cancer as well as in other conditions associated with immune activation. We present a case of a patient with advanced metastatic melanoma responding to the combination targeted therapy with dabrafenib and trametinib. The treatment was complicated by a fever that was accompanied by a marked rise in serum and urinary neopterin concentrations. Present case report illustrates not only the efficacy of combined targeted therapy, but also the utilization of neopterin measurements in the diagnosis and monitoring of pyrexia in patients with metastatic malignant melanoma.

Association of peripheral blood cell count-derived ratios, biomarkers of inflammatory response and tumor growth with outcome in previously treated metastatic colorectal carcinoma patients receiving cetuximab

Abstract The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In conclusion, in patients with metastatic colorectal carcinoma and predominantly liver metastases, the outcome of therapy in the advanced line setting was associated with initial hemoglobin level, a decrease of CEA concentration and initial presence of liver dysfunction. Urinary neopterin did not correlate with PBC-derived ratios, in contrast to CRP, but both urinary neopterin and serum CRP concentrations correlated with laboratory parameters of liver dysfunction.

Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: a case report and biomarker study

Abstract We report a patient who presented with synchronous second primary human epidermal growth factor receptor (HER)-2-positive breast cancer and rectal cancer that both required simultaneous neoadjuvant therapy. A modified regimen combining anti-HER-2 monoclonal antibody trastuzumab with chemotherapy and external beam radiation was selected. An organ-preserving surgical procedure was possible both in the breast and the rectum. Citrulline decreased rapidly after the start of the treatment, and then gradually returned to pre-treatment levels after the completion of chemoradiation. Urinary neopterin concentrations exhibited a fluctuating course. Both serum neopterin and C-reactive protein concentrations were more or less stable during the initial administration of trastuzumab, paclitaxel and carboplatin and then increased steeply during chemoradiation and subsequently declined to pre-treatment levels during the weekly trastuzumab administration. Changes were observed in the serum retinol concentrations. A decline in lymphocyte counts was accompanied by marked changes in peripheral blood cell count-derived ratios. The present case report demonstrates a successful combination of two neoadjuvant regimens in a patient with two synchronous different second primary tumors. Data from this case also illustrate the use of biomarkers for monitoring of intensive therapeutic regimens in medical and radiation oncology.

Peripheral blood leukocyte populations and urinary neopterin during chemotherapy in patients with breast cancer

Abstract The aim of the present study was to investigate serial changes in urinary neopterin and the populations of peripheral blood lymphocytes in breast cancer patients treated with primary chemotherapy. Thirty patients with breast cancer, including 20 patients undergoing primary chemotherapy treated with the combination of doxorubicin and cyclophosphamide with sequential administration of paclitaxel-based therapy (cohort A), and 10 patients presenting for first-line therapy of metastatic disease and treated with the combination of bevacizumab, taxane and carboplatin (cohort M) were studied. Healthy female blood donors served as control group. Significant differences were observed in baseline relative and absolute counts of peripheral blood lymphocyte subpopulations between both patient cohorts and controls. Significant changes of peripheral blood lymphocyte subpopulations were also observed during the course of chemotherapy. However, no significant changes of urinary neopterin concentrations and no correlation between urinary neopterin and peripheral blood lymphocyte counts were observed. In conclusion, present data demonstrate the presence of significant differences in peripheral blood leukocyte phenotype in breast cancer patients even before the start of primary chemotherapy. Significant changes were observed during the course of chemotherapy.

Association of urinary neopterin, neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios with long-term survival of patients with breast cancer

Abstract The immune response crucially determines the survival of patients with malignant tumors including breast carcinoma. The aim of the present study was to evaluate retrospectively an association of peripheral blood cell count (PBC)-derived ratios and urinary neopterin concentration with prognosis in breast cancer patients. Urinary neopterin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were retrospectively analyzed in a cohort of 474 breast cancer patients. NLR and PLR correlated positively with each other and negatively with LMR, but no correlation between neopterin concentrations and PBC-derived ratios was observed. Increased urinary neopterin concentration was a significant predictor of poor survival in patients with active disease, but PLR, NLR or LMR were not significantly associated with survival in multivariate analysis. In conclusion, increased urinary neopterin was a significant predictor of poor survival in patients with breast cancer and active disease.

Urinary neopterin, a non-invasive marker of mammalian cellular immune activation, is highly stable under field conditions.

Studying immunity and immune function in ecology and evolution requires field studies, but there has been a dearth of non-invasive markers of immune activation available for studying large wild mammals. Recently, we analytically and biologically validated the measurement of urinary neopterin (NEO), a biomarker of cellular immune activation, in captive macaques. However, applying this to free-ranging settings is complicated by issues involving sample collection, processing, storage, and transport. Here, we collected urine samples from captive macaques and undertook experiments simulating common field issues. We tested the effects on urinary NEO sample measurements following: dirt and faecal contamination; storage at room temperature; differences in processing and long-term storage methods (freezing, lyophilising, blotting onto filter paper); and freeze-thaw cycles. Our results show that concentrations of urinary NEO are highly stable – they are not affected by soil or faecal contamination, can be collected on filter paper and stored for many months frozen or lyophilised with minimal effect, and are resistant to multiple 24 hr freeze-thaws. With the addition of a biocidal preservative, concentrations are even stable at room temperature for long periods. Urinary NEO is remarkably resilient, and is highly suitable for non-invasive field studies of cellular immune responses in wild large mammals.

Correlations of neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios with biomarkers of atherosclerosis risk and inflammatory response in patients with a history of breast cancer

Abstract The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC)-derived ratios with neopterin concentration and biomarkers of atherosclerosis risk in patients with history of breast cancer. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were calculated in three cohorts of patients with a history of breast cancer and in controls. Significant differences were observed between PBC-derived ratios obtained from automated and manual counts. NLR and PLR were significantly higher and LMR was significantly lower in patients. NLR and PLR correlated positively with each other and negatively with LMR. NLR exhibited a significant correlation with age, glucose and C-reactive protein (CRP) concentrations, whereas LMR correlated negatively with CRP. With the exception of a correlation between LMR and urinary or serum neopterin concentrations in controls, no other correlation between neopterin concentrations and PBC-derived ratios was observed. NLR ≥3 was a significant predictor of poor survival, but neither urinary neopterin ≥205 μmol/mol creatinine, NLR ≥150 nor LMR ≥4.25 was significantly associated with survival. In conclusion, no consistent correlation was observed between urinary and serum neopterin concentrations and any of the PBC-derived ratios. In a cohort of breast cancer patients, a higher NLR predicted poor survival.

Citrulline as a biomarker of gastrointestinal toxicity in patients with rectal carcinoma treated with chemoradiation.

Gastrointestinal toxicity is the principal toxicity of chemoradiation in the treatment of rectal carcinoma. The assessment of this toxicity still relies mostly on the symptoms reported by the patient. Plasma citrulline, serum neopterin and urinary neopterin were followed weekly in 49 patients with rectal carcinoma during chemoradiation. Citrulline significantly (p<0.05) decreased while serum and urinary neopterin concentrations increased during therapy. Irradiated gut volume correlated significantly inversely with citrulline and positively with urinary neopterin. Statistically significant inverse correlations were also observed between urinary neopterin and plasma citrulline concentrations during the treatment. Urinary neopterin concentrations were significantly higher and citrulline concentrations were lower in patients who experienced grade ≥3 gastrointestinal toxicity. Citrulline represents a promising biomarker of gastrointestinal toxicity. Moreover, the volume of irradiated gut correlated with urinary neopterin concentrations and an association was observed between gastrointestinal toxicity evidenced by lower citrulline concentrations and systemic immune activation reflected in increased concentrations of urinary neopterin.

Urinary neopterin concentrations during radiotherapy for gynecological cancer

Abstract Neopterin is a biomarker of host response to neoplasia. In the present study, urinary neopterin was determined during the course of (chemo)radiation in ten patients with gynecological tumors (nine patients with cervical carcinoma and one patient with carcinoma of the vulva). Baseline urinary neopterin concentrations were, generally, above the normal range. Neopterin concentrations were relatively stable during the first 5 weeks of combined (chemo)radiation. Marked peaks of neopterin concentrations reflected the emergence of complications. Neopterin could represent a useful biomarker for the assessment of the condition of the patients during this aggressive therapy.

Urinary neopterin levels in patients with thyroid cancer.

Increased urinary neopterin concentrations have been described in many cancers. We aimed to evaluate the urinary neopterin levels in thyroid cancer. Sixty-nine patients with thyroid cancer, 76 patients with benign thyroid pathology and 33 healthy subjects were evaluated. First morning urine samples were collected from the patients and normal subjects for neopterin and creatinine measurement and stored at -80°C until analysed. Neopterin levels were 149.3 (15.2-1,602.2) μmol/mol creatinine in the malignant group, 32 (5.2-275.6) μmol/mol creatinine in the benign group and 9.2 (2.7-78.7) μmol/mol creatinine in normal subjects (p≤0.001). Urinary neopterin levels were significantly higher in patients with thyroid cancer than patients with benign thyroid pathologies and normal subjects. Also the patients with benign thyroid pathologies had a higher urinary neopterin level than the normal subjects. Malignant group was divided to two groups; patients with/without chronic thyroiditis (confirmed histologically). There were 22 (31.9 %) patients with and 47 (68.1%) patients without chronic thyroiditis. Urinary levels of neopterin didn't differ in both groups (168.6 (21.3-716.8) μmol/mol creatinine and 135.3 (15.2-1,602.2) μmol/mol creatinine respectively; p=0.381). Urinary neopterin levels are high in thyroid cancer patients independently from the presence of chronic thyroiditis.

Systemic immune response and peripheral blood cell count in patients with a history of breast cancer

Abstract The aim of the present study was to evaluate the association between changes in peripheral blood cell count and neopterin concentrations in patients with a history of breast cancer. Peripheral blood cell count, serum ferritin, serum neopterin and urinary neopterin concentrations were determined in 61 patients with a history of breast cancer and 74 control subjects. Hemoglobin, relative lymphocyte count and absolute lymphocyte count were lower, and relative neutrophil count, ferritin and serum neopterin concentrations were significantly higher in breast cancer patients than in controls. Compared to controls, the difference in hemoglobin concentration was statistically significant only in patients with active disease. Significant negative correlations were observed between urinary neopterin and hemoglobin as well as between serum neopterin and relative lymphocyte counts in breast cancer patients. Increased ferritin concentrations were associated with a history of hypertension, but higher absolute lymphocyte counts were associated with hypertension only in subjects without history of cancer. In conclusion, in patients with a history of breast cancer, anemia is associated with disease activity and systemic immune activation. Ferritin concentrations are increased in subjects with hypertension.

Risk factors of atherosclerosis in patients with history of breast cancer

Abstract The aim of the present study was to evaluate the prevalence of the risk factor of atherosclerosis in patients with history of breast cancer. C-reactive protein, lipoprotein (a), cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, homocysteine, fibrinogen, glucose, magnesium, uric acid, and urinary albumin were determined by routine methods in 61 patients with history of breast cancer and 74 control subjects. Urinary neopterin and creatinine concentrations were measured by high-performance liquid chromatography, and intima-media thickness was determined sonographically. Breast cancer patients were significantly older and also had higher systolic blood pressure, glycosylated hemoglobin, lipoprotein (a), serum neopterin, and intima-media thickness. Serum HDL cholesterol and magnesium concentrations were significantly higher in controls compared with patients. Differential patterns of associations between the risk factors of atherosclerosis were observed in patients with history of breast cancer compared with controls. In conclusion, the prevalence of risk factors of atherosclerosis is high in patients with history of breast cancer. Differential associations between risk factors suggest possible differences in the pathogenesis of atherosclerosis in breast cancer patients and controls.

The significance of neopterin and biopterin concentrations at presentation in haematological malignancies.

Urinary neopterin and biopterin concentrations were measured in 32 healthy controls and 53 patients with newly diagnosed haematological malignancies classified and staged by accepted criteria. The neopterin concentrations were only significantly raised in chronic lymphocytic leukaemia at stages III-IV. Total biopterin concentrations after oxidation with iodine at acid pH were decreased in chronic lymphocytic leukaemia stages O-II, multiple myeloma, and acute myeloid leukaemia but not in chronic lymphocytic leukaemia stages III-IV. Although of research interest, neopterin concentrations proved of little prognostic value at presentation, but taken with the biopterin concentration they may be useful for the assessment of tumour activity.

Day-to-day cause–effect relations between cellular immune activity, fatigue and mood in a patient with prior breast cancer and current cancer-related fatigue and depression

This study of a breast cancer patient with cancer-related fatigue (CaRF) and depression investigated the bidirectional cause-effect relations between cellular immune activity, fatigue and mood during 'life as it is lived'. The 49-year-old patient (breast cancer diagnosis 5 years earlier, severe CaRF and increase in depressiveness since then) collected her entire urine for 28 days in 12-h intervals (from 8 p.m. to 8 a.m. and from 8 a.m. to 8 p.m.; total: 55 measurements) for the determination of urinary neopterin (immune activation marker) and creatinine levels using HPLC. Furthermore, she completed questionnaires twice each day (at approx. 8 a.m. and 8 p.m.), which yielded information on mood (3-Skalen-Eigenschaftswörterliste [EWL]) and fatigue levels (visual analog scale [VAS]). Cross-correlational analyses showed complex connections between urinary neopterin concentrations and mood and fatigue in terms of direction of effect, temporal delay and response pattern. Increases in urinary neopterin levels significantly preceded increases in fatigue intensity with a temporal delay of 60-72h (lag 5: r=0.298; p=0.027), whereas increases in positive mood co-occurred with neopterin level increases (lag 0: r=+0.302; p=0.025) and preceded decreases in neopterin concentrations with a temporal delay of 132-144h (lag 11: r=-0.323; p=0.017). These results confirm and extend our previous findings and show that in order to obtain an adequate understanding of the dynamic relations among cancer-related variables, the characteristics of everyday-life conditions need to be considered.

Neopterin Concentration as an Index of Disease Activity in Crohn’s Disease and Ulcerative Colitis

Neopterin, a pyrazino-[2,3-d]-pyrimidine compound, is a metabolite of cyclic guanosine monophosphate that is released by activated T lymphocytes and macrophages after induction by γ interferon. We sought to determine whether neopterin concentration in stool, serum, or urine is a useful marker of disease activity in patients with Crohn's disease or ulcerative colitis. We prospectively studied 70 outpatients (33 M, 37 F, aged 39.2 ± 14.0 y) with Crohn's disease (33 clinically in remission, 37 active), 52 outpatients (29 M, 23 F, aged 39.8 ± 12.2 y) with ulcerative colitis (29 clinically in remission, 23 active), and 141 healthy control subjects. Fecal, serum, and urine samples were analyzed for neopterin concentration and other analytes of interest. The following clinical indices were calculated at enrollment: for Crohn's disease, the Capetown Index and Harvey Bradshaw Index; for ulcerative colitis, Simple Clinical Colitis Activity Index, Disease Activity Index, and endoscopic disease severity (rated on a scale of 0 to 3). Crohn's disease was considered active if the Harvey Bradshaw Index was ≥ 5, and ulcerative colitis was considered active if the Simple Clinical Colitis Activity Index was >3. Among Crohn's disease patients, fecal neopterin was higher in those with either clinically active (96.0 ng/g) or inactive (87.2 ng/g) disease than in control subjects (12.0 ng/g; P<0.05; inactive or active disease vs. controls). For ulcerative colitis patients, fecal neopterin concentration was higher in those with active (135.2 ng/g) disease than in those with inactive disease (62.7 ng/g; P<0.05) or healthy controls (12.0 ng/g; P<0.05). Neither serum nor urine neopterin concentrations were increased in patients with active inflammatory bowel disease. Nonsignificant trends toward greater fecal neopterin concentration were observed with increased colonic disease involvement, although not with endoscopic severity or clinical disease activity indices. Fecal neopterin concentration is increased in patients with clinically active or inactive Crohn's disease and in patients with clinically active ulcerative colitis when compared with controls, and therefore represents a new biomarker for disease activity.