Agonistic anti-DCIR antibody inhibits ITAM-mediated inflammatory signaling and promotes immune resolution.

DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies, suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immunoreceptor tyrosine-based inhibitory motifs and recruitment of SH2 containing protein tyrosine phosphatase-2 for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR-knock-in mouse model, we validated the antiinflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.

Nasogastric bridles are associated with improved tube-related outcomes in children.

OBJECTIVE: To compare tube-related outcomes in children with standard tape vs nasal bridle securement of nasogastric tubes (NGTs). STUDY DESIGN: This was a single-center, retrospective, correlational study of outcomes from the time of NGT placement until full oral feeds or durable-tube placement. Outcomes of interest included NGT dislodgments, length of stay, emergency department (ED) encounters, radiographic exposures, and adverse skin outcomes. Negative binomial regression and logistic regression were used to analyze differences between groups. RESULTS: Five hundred eighty-two children had NGTs secured traditionally (43% female; age at therapy initiation of 2.6 months [SD 8.1]), and 173 received nasal bridles (55.5% female; age at therapy initiation of 8.4 months [SD 11.8]). Children with bridled NGTs were 16.67 times less likely to experience one or more dislodgments (odds ratio [OR] = 0.06; 95% CI, 0.04-0.09); 2.5 times less likely to have one more ED visit (OR = 0.4; 95% CI, 0.19-0.82), and 4.76 times less likely to require one more radiographic exposure (OR = 0.21; 95% CI, 0.14-0.33) than unbridled children (all P values < 0.02). The mean initial hospital length of stay was 28 and 54 days in the bridled-NGT and standard-care groups, respectively (P < 0.001). Overall, 62.4% children with bridled NGTs and 77.1% children with unbridled NGTs progressed to full oral feedings and discontinued therapy (P < 0.001). Adverse skin outcomes were rare in both groups. CONCLUSION: Children with bridled NGTs experienced fewer dislodgments, hospital days, ED encounters, and radiographic exposures than unbridled NGTs. Most children in both groups progressed to full oral feedings.

Validity and Reliability of the Antepartum Gastrointestinal Symptom Assessment Instrument.

OBJECTIVE: To examine the psychometric properties of the nine-item Antepartum Gastrointestinal Symptom Assessment (AP-GI-SA) instrument. DESIGN: Single-group prospective design. SETTING: Urban prenatal clinic serving a diverse population. PARTICIPANTS: Convenience sample of 45 pregnant women. METHODS: Participants completed the AP-GI-SA before a scheduled prenatal care appointment. We used Bayesian structural equation modeling to evaluate the construct validity of the scale and assessed known-groups validity. We assessed reliability through maximal reliability coefficient estimate and measured internal consistency with Cronbach's alpha coefficient. RESULTS: Participants completed the instrument in 2 minutes or less. Construct validity was supported by confirmatory factor analysis (posterior predictive p value = 0.49, gamma-hat = 0.970, and root mean square error of approximation = 0.065), which indicated that the single-factor model is a plausible data-generative model for GI symptoms. The maximal reliability coefficient of 0.75 and Cronbach's alpha coefficient of 0.67 supported reliability. Average AP-GI-SA scores were the highest for women in the third trimester. Of all nine GI symptoms, heartburn in the third trimester received the highest score. CONCLUSION: Our findings provide preliminary support for the validity and reliability of the AP-GI-SA. The instrument may be used as a measure in intervention studies where GI symptoms of pregnancy are an outcome. The AP-GI-SA could also be useful in clinical settings to quickly evaluate GI symptoms.

CRISPR/Cas9-targeting of CD40 in hematopoietic stem cells limits immune activation mediated by anti-CD40.

Inflammatory bowel diseases (IBD) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. IBD is diagnosed around 1 in 1000 individuals in Western countries with globally increasing incident rates. Association studies have identified hundreds of genes that are linked to IBD and potentially regulate its pathology. The further dissection of the genetic network underlining IBD pathogenesis and pathophysiology is hindered by the limited capacity to functionally characterize each genetic association, including generating knockout animal models for every associated gene. Cutting-edge CRISPR/Cas9-based technology may transform the field of IBD research by efficiently and effectively introducing genetic alterations. In the present study, we used CRISPR/Cas9-based technologies to genetically modify hematopoietic stem cells. Through cell sorting and bone marrow transplantation, we established a system to knock out target gene expression by over 90% in the immune system of reconstituted animals. Using a CD40-mediated colitis model, we further validated our CRISPR/Cas9-based platform for investigating gene function in experimental IBD. In doing so, we developed a model system that delivers genetically modified mice in a manner much faster than conventional methodology, significantly reducing the time from target identification to in vivo target validation and expediting drug development.

Chronic Stress and Ovarian Function in Female Childhood Cancer Survivors.

OBJECTIVES: To explore the relationships among perceived stress, biomarkers of hypothalamic-pituitary-adrenal (HPA) activity, gonadotropin levels, and anti-Müllerian hormone (AMH) in female childhood cancer survivors (CCSs). SAMPLE & SETTING: 24 female CCSs from the Royal Hospital for Sick Children in Edinburgh, Scotland, were included in the study. METHODS & VARIABLES: Perceived stress was measured using the Perceived Stress Scale. HPA activity was measured using salivary cortisol and hair cortisol. Ovarian function was measured using serum gonadotropin levels and serum AMH levels. Latent growth curve modeling was used to determine diurnal cortisol slope and intercept. Bayesian structural equation modeling was used to explore the relationship among perceived stress, biomarkers of HPA activity, and ovarian function. RESULTS: The authors found an inverse association between perceived stress and ovarian function and a positive association between biomarkers of HPA activity and ovarian function. IMPLICATIONS FOR NURSING: Further research is needed to understand factors contributing to risk for post-treatment reproductive dysfunction in female CCSs.

Exploring the Ovarian Reserve Within Health Parameters: A Latent Class Analysis.

The process of ovarian aging is influenced by a complex and poorly understood interplay of endocrine, metabolic, and environmental factors. The purpose of this study was to explore the feasibility of using latent class analysis to identify subgroups based on cardiometabolic, psychological, and reproductive parameters of health and to describe patterns of anti-Müllerian hormone levels, a biomarker of the ovarian reserve, within these subgroups. Sixty-nine lean (body mass index [BMI] ⩽ 25 kg/m2) and severely obese (BMI ⩾ 40 kg/m2) postpartum women in Edinburgh, Scotland, were included in this exploratory study. The best fitting model included three classes: Class 1, n = 23 (33.5%); Class 2, n = 30 (42.2%); Class 3, n = 16 (24.3%). Postpartum women with lower ovarian reserve had less favorable cardiometabolic and psychological profiles. Examining the ovarian reserve within distinct subgroups based on parameters of health that affect ovarian aging may facilitate risk stratification in the context of ovarian aging.

Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women.

BACKGROUND: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. OBJECTIVES: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1ß production. METHODS: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1ß production was quantified. Medical record review determined timing of birth. RESULTS: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1ß production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1ß production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). DISCUSSION: Women with GG genotype may be at risk for earlier birth because of diminished IL-1ß inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

An Online Educational Program Improves Pediatric Oncology Nurses' Knowledge, Attitudes, and Spiritual Care Competence.

This study evaluated the potential impact of an online spiritual care educational program on pediatric nurses' attitudes toward and knowledge of spiritual care and their competence to provide spiritual care to children with cancer at the end of life. It was hypothesized that the intervention would increase nurses' positive attitudes toward and knowledge of spiritual care and increase nurses' level of perceived spiritual care competence. A positive correlation was expected between change in nurses' perceived attitudes toward and knowledge of spiritual care and change in nurses' perceived spiritual care competence. A prospective, longitudinal design was employed, and analyses included one-way repeated-measures analysis of variance, linear regression, and partial correlation. Statistically significant differences were found in nurses' attitudes toward and knowledge of spiritual care and nurses' perceived spiritual care competence. There was a positive relationship between change scores in nurses' attitudes toward and knowledge of spiritual care and nurses' spiritual care competence. Online spiritual care educational programs may exert a lasting impact on nurses' attitudes toward and knowledge of spiritual care and their competence to provide spiritual care to children with cancer at the end of life. Additional studies are required to evaluate the direct effects of educational interventions patient outcomes.

Anti-Müllerian Hormone Levels and Urinary Cortisol in Women With Chronic Abdominal Pain.

OBJECTIVE: To explore the association of hypothalamic-pituitary-adrenal activity with ovarian functioning in women with and without chronic abdominal pain (CAP). DESIGN AND SETTING: A secondary data analysis was performed with data from female participants in a natural history protocol at the National Institutes of Health. PARTICIPANTS: A total of 36 women (age range = 19-39 years, mean = 27.11 years) were included in the study. METHODS: This pilot study was conducted with a subset of participants enrolled in a natural history protocol conducted in the Hatfield Clinical Research Center at the National Institutes of Health. The parent study included participants with and without CAP who provided a 5-hour urine sample for determination of cortisol levels and serum samples for determination of circulating levels of cortisol, luteinizing hormone, and follicle-stimulating hormone. CAP was defined as presence or absence of chronic pain for at least 6 months and was determined via self-report. RESULTS: Anti-Müllerian hormone (AMH) concentrations declined significantly with age as expected. When AMH levels were dichotomized as normal or abnormal (defined as higher or lower than age-specific normative ranges, respectively), there were significant associations between abnormal AMH levels and CAP and urine cortisol levels. Participants with CAP or low urine cortisol levels were significantly more likely to have abnormal AMH levels. CONCLUSION: Results suggest that chronic abdominal pain and hypothalamic-pituitary-adrenal dysregulation may be associated with abnormal AMH levels.

Feasibility of Hair Collection for Cortisol Measurement in Population Research on Adolescent Health.

BACKGROUND: Black-White disparities in adolescent health are widespread and thought to be explained, in part, by exposure to chronic stress. Cortisol assayed from hair is increasingly recognized as a valid and reliable measure for chronic physiological stress, but the feasibility of collecting hair among large probability samples of diverse adolescents is unknown. PURPOSE: The aim of the study was to investigate participation in hair collection for cortisol analyses in a probability sample of racially and socioeconomically diverse adolescents, including the extent to which sociodemographic factors and adverse exposures were associated with participation. METHODS: The study included a probability sample of 516 adolescents conducted in conjunction with a prospective cohort study on adolescent health. Data were collected over 1 week via in-home interviews, ecological momentary assessment, global positioning system methods, and in-home hair collection at the end of the week. RESULTS: Of the 516 eligible youth, 471 (91.3%) participated in the hair collection. Of the 45 youth who did not provide hair samples, 18 had insufficient hair, 25 refused, and 2 did not participate for unknown reasons. Multivariable logistic regression results indicated that non-Hispanic Black youth were less likely than their non-Hispanic White peers to participate due to insufficient hair or refusal (OR = 0.24, 95% CI [0 .09, 0.60]). Despite lower rates of participation, the proportion of Black youth in the participating sample was representative of the study area. No significant differences in participation were found by other sociodemographic characteristics or adverse exposures. CONCLUSIONS: Hair collection for cortisol measurement is feasible among a probability sample of racially and socioeconomically diverse adolescents. Hair cortisol analyses may accelerate research progress to understand the biological and psychosocial bases of health disparities.

Ibuprofen ameliorates fatigue- and depressive-like behavior in tumor-bearing mice.

AIMS: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. MAIN METHODS: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. KEY FINDINGS: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1ß and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. SIGNIFICANCE: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF.

Integrating emerging areas of nursing science into PhD programs.

The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2010 American Association of Colleges of Nursing Position Statement "The Research-Focused Doctoral Program in Nursing: Pathways to Excellence," Idea Festival Advisory Committee members focused on emerging areas of science and technology that impact the ability of research-focused doctoral programs to prepare graduates for competitive and sustained programs of nursing research using scientific advances in emerging areas of science and technology. The purpose of this article is to describe the educational and scientific contexts for the Idea Festival, which will serve as the foundation for recommendations for incorporating emerging areas of science and technology into research-focused doctoral programs in nursing.

Emerging areas of science: Recommendations for Nursing Science Education from the Council for the Advancement of Nursing Science Idea Festival.

The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee (IFAC) to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2005 National Research Council report Advancing The Nation's Health Needs and the 2010 American Association of Colleges of Nursing Position Statement on the Research-Focused Doctorate Pathways to Excellence, the IFAC specifically addressed the capacity of PhD programs to prepare nursing scientists to conduct cutting-edge research in the following key emerging and priority areas of health sciences research: omics and the microbiome; health behavior, behavior change, and biobehavioral science; patient-reported outcomes; big data, e-science, and informatics; quantitative sciences; translation science; and health economics. The purpose of this article is to (a) describe IFAC activities, (b) summarize 2014 discussions hosted as part of the Idea Festival, and (c) present IFAC recommendations for incorporating these emerging areas of science and technology into research-focused doctoral programs committed to preparing graduates for lifelong, competitive careers in nursing science. The recommendations address clearer articulation of program focus areas; inclusion of foundational knowledge in emerging areas of science in core courses on nursing science and research methods; faculty composition; prerequisite student knowledge and skills; and in-depth, interdisciplinary training in supporting area of science content and methods.

Emerging areas of nursing science and PhD education for the 21(st) century: response to commentaries.

We respond to commentaries from the American Academy of Nursing, the American Association of Colleges of Nursing, and the National Institute of Nursing Research on our thoughts about integrating emerging areas of science into nursing PhD programs. We identify areas of agreement and focus our response on cross-cutting issues arising from cautions about the unique focus of nursing science and how best to proceed with incorporation of emerging areas of science into nursing PhD programs.

Educating future nursing scientists: Recommendations for integrating omics content in PhD programs.

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science's Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals.

Losartan treatment attenuates tumor-induced myocardial dysfunction.

UNLABELLED: Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. METHODS AND RESULTS: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. CONCLUSIONS: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.

Bidirectional psychoneuroimmune interactions in the early postpartum period influence risk of postpartum depression.

More than 500,000 U.S. women develop postpartum depression (PPD) annually. Although psychosocial risks are known, the underlying biology remains unclear. Dysregulation of the immune inflammatory response and the hypothalamic-pituitary-adrenal (HPA) axis are associated with depression in other populations. While significant research on the contribution of these systems to the development of PPD has been conducted, results have been inconclusive. This is partly because few studies have focused on whether disruption in the bidirectional and dynamic interaction between the inflammatory response and the HPA axis together influence PPD. In this study, we tested the hypothesis that disruption in the inflammatory-HPA axis bidirectional relationship would increase the risk of PPD. Plasma pro- and anti-inflammatory cytokines were measured in women during the 3rd trimester of pregnancy and on Days 7 and 14, and Months 1, 2, 3, and 6 after childbirth. Saliva was collected 5 times the day preceding blood draws for determination of cortisol area under the curve (AUC) and depressive symptoms were measured using the Edinburgh Postpartum Depression Survey (EPDS). Of the 152 women who completed the EPDS, 18% were depressed according to EDPS criteria within the 6months postpartum. Cortisol AUC was higher in symptomatic women on Day 14 (p=.017). To consider the combined effects of cytokines and cortisol on predicting symptoms of PPD, a multiple logistic regression model was developed that included predictors identified in bivariate analyses to have an effect on depressive symptoms. Results indicated that family history of depression, day 14 cortisol AUC, and the day 14 IL8/IL10 ratio were significant predictors of PPD symptoms. One unit increase each in the IL8/IL10 ratio and cortisol AUC resulted in 1.50 (p=0.06) and 2.16 (p=0.02) fold increases respectively in the development of PPD. Overall, this model correctly classified 84.2% of individuals in their respective groups. Findings suggest that variability in the complex interaction between the inflammatory response and the HPA axis influence the risk of PPD.

Storage Conditions and Passages Alter IL-6 secretion in C26 adenocarcinoma cell lines.

The C26 adenocarcinoma tumor line is frequently used to establish peripheral tumors in mice for the study of cancer cachexia and cancer-related fatigue. Recently, we have noticed a progressive decline in the effects of tumor growth on our biological and behavioral measures in the tumor-bearing mice. Therefore, we compared effects of three aliquots of the C26 tumor cell line that differed in storage condition and number of passages on cytokine secretion, tumor growth, weight loss and fatigue behavior. Three aliquots of the C26 tumor line were selected as alpha (α), beta (ß), and gamma (γ). Aliquot α was an original C26 stock line that had been stored at -80°C. Aliquot ß was stored in liquid nitrogen. Aliquot γ was taken from aliquot ß and passaged three times. The three aliquots of the C26 tumor line showed differences in IL-6 mRNA and protein secretion in vitro, with aliquot ß showing the greatest IL-6 secretion. These differences were mirrored in vivo. Plasma IL-6 levels were elevated in all tumor bearing mice but was greatest in group ß mice. Carcass weight was decreased in all three tumor groups. Brain expression of IL-1ß mRNA was greatest in group ß and group ß demonstrated the greatest decline in running activity at day 19. Storage conditions and number of passages influence C26 tumor cell secretion of cytokines.Variations in C26 aliquots may explain differences observed between laboratories using the same cell line.We recommend always storing cell lines in liquid nitrogen and limiting the number of passages before use in experiments.

Fluoxetine prevents the development of depressive-like behavior in a mouse model of cancer related fatigue.

Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine.