Blood Immune Cell Counts Research Articles

A novel exosome-like nanovesicles from Cordyceps militaris potentiate immunomodulatory and anti-tumor effect by reprogramming macrophages

AimsFungi-derived exosome-like nanovesicles (ENs) are emerging as a highly promising class of nanoparticles, particularly noted for their cost-effective production. However, their impact on immune regulation and their potential as anti-tumor agents need further exploration. Our study specifically focused on the investigation of the immunomodulatory and anti-tumor properties of ENs derived from Cordyceps militaris, an edible fungus that had achieved large-scale commercial production, referred to as CMDENs. Main methodsThe ENs of C. militaris were collected through ultra-high-speed centrifugation, followed by characterization of their physicochemical properties and contents. Subsequently, the biological distribution of these vesicles was investigated using in vivo fluorescence imaging experiments. Finally, the immune activation and polarization of macrophages were examined through both in vitro and in vivo experiments. Key findingsHerein, we presented the discovery of CMDENs that were rich in proteins, lipids, flavonoids and alkaloids. Immunomodulatory experiments conducted in vivo demonstrated that CMDENs exhibited protective effects against cyclophosphamide-induced immunosuppression in mice by significantly enhancing macrophage phagocytosis and peripheral blood immune cell counts. Moreover, CMDENs effectively induced the polarization of M0- and M2-like macrophages toward M1-like phenotype by activating MAPKs signaling pathway. Notably, CMDENs exhibited remarkable capabilities in inhibiting tumor growth by reprogramming tumor-associated macrophages and activating tumor-infiltrating T lymphocytes, without any observed toxicity in mice bearing tumors. SignificanceOur research suggested that CMDENs possessed the potential to be explored as a nano-immunomodulatory agent for cancer.

Evaluation of plant commercial feed additives for equine cyathostomin control

The increasing emergence of anthelmintic-resistant parasitic isolates prompts us to reassess the management of intestinal strongylosis in horses. Additionally, societal demand is shifting toward reducing the use of chemical treatments, aligning with environmentally-friendly practices and the exploration of natural alternatives. In this context, we provide an initial view of the antiparasitic activity and the effect on immune circulating blood cells of three commercialized plant-based feed additives in ponies. Three treatments, based either on mugwort (Artemisia vulgaris), echinacea (Echinacea purpurea) or curcumin (Curcuma longa) were administrated to 18 (six per treatment) Welsh female ponies naturally infected with cyathostomins to mimic their practical use in farming conditions. Another group of six untreated ponies was used as a control. Fecal egg count (FEC), the larval development percentage and the number of red blood cells, lymphocytes, monocytes, neutrophils, eosinophils and basophils were measured the first and the last day of each treatment, and compared with those characterizing the control group. None of the three treatments showed a significant effect on the studied parameters. Moreover, the efficacy of treatments, measured from the FEC reduction compared to the control group, was weak (≤ 38.6 %). Therefore, these results do not support the practical use of these additives in equine farming, even if the determination of Cohen's d values associated with the three treatments revealed some incidences on FEC and blood immune cell counts, as well as on larval development for mugwort.

Differences and Risk Factors of Peripheral Blood Immune Cells in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a respiratory disorder characterized by chronic intermittent hypoxia and fragmented sleep, leading to inflammatory response and oxidative stress. However, the differences in immune inflammatory response in OSA patients with different severity remain unclear. This study aims to examine the differences in peripheral blood immune cells and their risk factors in OSA patients. A total of 277 snoring patients from the Sleep Respiratory Disorder Monitoring Center of Zhongnan Hospital of Wuhan University were recruited in this study. According to the diagnosis and severity criteria of OSA, the included patients were further divided into simple snoring, mild, moderate, and severe groups. Peripheral blood immune cell counts including white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells, platelets, and polysomnography indicators were collected from the patients. Compared with simple snoring patients, the OSA patients had increased circular monocyte and basophil count levels. In addition, correlation analysis results indicated that monocyte count was positively associated with chronic obstructive pulmonary disease (COPD), smoking, apnea-hypopnea index (AHI), the longest apnea duration, and Oxygen desaturation index (ODI), and negatively correlated with average SpO2 in snoring patients. Finally, multiple linear regression analysis revealed that AHI, COPD, smoking, and maximum heart rate were independent predictors of monocyte count. OSA patients had a significant increase in their peripheral blood monocyte count. AHI, COPD, smoking, and maximum heart rate were risk factors for increased peripheral blood monocyte count in OSA patients. These findings suggest that peripheral blood monocytes can be considered an inflammatory biomarker of OSA.

Correlation of Oral Microbiota With Different Immune Responses to Antiretroviral Therapy in People Living With HIV

Abstract Both HIV infection and antiretroviral therapy (ART) affect the oral microbiome. Whether successful treatment with ART in people living with HIV (PLWH), which leads to a significant decline in viral loads and immune reconstitution, is associated with changes in or recovery of the oral microbiome remains unknown. Therefore, we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls (HCs). Among the 118 PLWH, 18 immunological nonresponders (INRs; <200 CD4+ T cells/μL) and 30 immunological responders (IRs; ≥500 CD4+ T cells/μL) were identified. The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples. Relative abundance of bacterial genera was compared between IRs and INRs, and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated. The INR group showed lower alpha diversity than the IR and HC groups, which displayed similar alpha diversity. The genera Alloprevotella, Prevotella and Neisseria were more abundant in PLWH than in HCs, whereas the genera Rothia, Streptococcus and Fusobacterium were more abundant in HCs than in PLWH. The genus Rothia was more abundant in the INR group, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus were more abundant in the IR group. The genera Rothia and Alloprevotella were negatively and positively associated with CD4+ T cell counts, respectively. Thus, an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART, whereas Prevotella, Alloprevotella, Porphyromonas and Haemophilus are associated with favorable outcomes.

Magnesium supplementation modulates T-cell function in people with type 2 diabetes and low serum magnesium levels.

Low magnesium levels, which are common in people with type 2 diabetes, are associated with increased levels of pro-inflammatory molecules. It is unknown whether magnesium supplementation decreases this low-grade inflammation in people with type 2 diabetes. We performed a multidimensional immunophenotyping to better understand the effect of magnesium supplementation on the immune system of people with type 2 diabetes and low magnesium levels. Using a randomized, double-blind, placebo-controlled, two-period, cross-over study, we compared the effect of magnesium supplementation (15 mmol/day) to placebo on the immunophenotype including whole blood immune cell counts, T-cell and CD14+ monocyte function after ex vivo stimulation, and the circulating inflammatory proteome. We included 12 adults with insulin-treated type 2 diabetes (7 males, mean±SD age 67±7 years, BMI 31±5 kg/m2, HbA1c 7.5±0.9 %) and low magnesium levels (0.73±0.05 mmol/l). Magnesium treatment significantly increased serum magnesium and the urinary magnesium excretion, when compared to placebo. The IFN-γ production from PMA/ionomycin stimulated CD8+ T-cells and T-helper 1 cells, as well as the IL4/IL5/IL13 production from T-helper 2 cells was lower after treatment with magnesium compared to placebo. Magnesium supplementation did not affect immune cell numbers, ex vivo monocyte function and circulating inflammatory proteins, although we found a tendency for lower high sensitive CRP levels after magnesium supplementation compared to placebo. In conclusion, magnesium supplementation modulates the function of CD4+ and CD8+ T-cells in people with type 2 diabetes and low serum magnesium levels.

Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC) affect approximately 10% of convalescent patients. The spectrum of symptoms is broad and heterogeneous with fatigue being the most often reported sequela. Easily accessible blood biomarkers to determine PASC severity are lacking. Thus, our study aimed to correlate immune phenotypes with PASC across the severity spectrum of COVID-19. A total of 176 originally immunonaïve, convalescent COVID-19 patients from a prospective cohort during the first pandemic phase were stratified by initial disease severity and underwent clinical, psychosocial, and immune phenotyping around 10weeks after first COVID-19 symptoms. COVID-19-associated fatigue dynamics were assessed and related to clinical and immune phenotypes. Fatigue and severe fatigue were commonly reported irrespective of initial COVID-19 severity or organ-specific PASC. A clinically relevant increase in fatigue severity after COVID-19 was detected in all groups. Neutralizing antibody titers were higher in patients with severe acute disease, but no association was found between antibody titers and PASC. While absolute peripheral blood immune cell counts in originally immunonaïve PASC patients did not differ from unexposed controls, peripheral CD3+CD4+ T cell counts were independently correlated with fatigue severity across all strata in multivariable analysis. Patients were at similar risk of self-reported PASC irrespective of initial disease severity. The independent correlation between fatigue severity and blood T cell phenotypes indicates a possible role of CD4+ T cells in the pathogenesis of post-COVID-19 fatigue, which might serve as a blood biomarker.

Association between immune cells in peripheral blood and psychiatric symptoms.

There are bidirectional associations between immunological dysfunction and psychiatric symptoms. However, the associations between the levels of immune cells in the peripheral blood and psychiatric symptoms remain unclear. The present study aimed to evaluate levels of immune cells in peripheral blood in people with positive psychiatric symptoms. This retrospective study analyzed data from routine blood tests and psychopathology and sleep quality assessments. Data were compared between a group of 45 patients with de novo psychological symptoms and 225 matched controls. Patients with psychiatric symptoms had higher white blood cell and neutrophil counts compared with controls. However, in a subgroup analysis, neutrophil counts were significantly higher than in controls only in patients with multiple psychiatric symptoms. Furthermore, monocyte counts were significantly higher in patients with multiple psychiatric symptoms than in controls. Further, sleep quality was lower in patients with psychiatric symptoms than in controls. White blood cell and neutrophil counts in the peripheral blood of patients with psychiatric symptoms were significantly higher and sleep quality was significantly lower than in controls. Participants with multiple psychiatric symptoms showed more significant differences in peripheral blood immune cell counts than other subgroups. These results provided evidence for the relationship between psychiatric symptoms, immunity, and sleep.

Identification of PFKFB2 as a key gene for the transition from acute to old myocardial infarction in peripheral blood.

This study aims to analyze the gene expression profile of peripheral blood in different stages of myocardial infarction (MI) by transcriptome sequencing, and to study the gene expression characteristics of peripheral blood after MI. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify genes and modules associated with old myocardial infarction (OMI). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were applied to analyze the potential functions of genes. Hub genes were identified by Random Forest Classifier. CIBERSORT was used to provide an estimate of the abundance of 22 immune cells in peripheral blood. Quantitative polymerase chain reaction (qPCR) was used to detect gene expression levels in clinical samples. The cellular components (CC) of peripheral blood were counted by an automatic hematology analyzer. Through differential gene analysis and co-expression network analysis, 11 candidate genes were obtained. A random forest classifier identified 10 hub genes. Immune cell distribution of peripheral blood was found that T cell CD4 memory resting, NK cells resting, Dendritic cells activated, Mast cells resting, Monocytes and Neutrophils were correlated with OMI. Spearman correlation analysis found that PFKFB2 is related to the above immune cells. Low expression of PFKFB2 in peripheral blood of OMI was detected in clinical samples, and the relationship between PFKFB2 and peripheral blood immune cell counts was analyzed, which showed monocytes were associated with PFKFB2 in our study. PFKFB2 was low expressed in OMI, and related to the distribution of immune cells. PFKFB2 may play a key role in reflecting the transition from AMI to OMI, and predicting the distribution of immune cells, which provided a new perspective for improving myocardial fibrosis and adverse remodeling.

Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients.

BackgroundBiomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS).MethodsSerum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX.ResultsPatients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25, P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14, P=0.010), IL-18 (HR 2.00, P=0.020), and MIP-1β (HR 0.51, P=0.025) after one cycle of FOLFIRINOX showed correlations with OS.ConclusionsCirculating IL-1RA, IL-7, IL-18, and MIP-1β concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies.

Small molecule tyrosine kinase inhibitors modulated blood immune cell counts in patients with oncogene-driven NSCLC

BackgroundLack of biomarkers and in vitro models has contributed to inadequate understanding of the mechanisms underlying the inferior clinical response to immune checkpoint inhibitors (ICIs) in patients with oncogene-driven non-small cell lung cancer (NSCLC).MethodsThe effect of small molecule tyrosine kinase inhibitors (TKIs) on peripheral blood mononuclear cells (PBMCs) in 34 patients with oncogene-driven NSCLC (cohort A) was compared with those from 35 NSCLC patients without oncogene-driven mutations received ICI (cohort B) or from 22 treatment-naïve NSCLC patients (cohort C). Data for each blood biomarker were summarized by mean and standard deviation and compared by Wilcoxon rank sum tests or Kruskal-Wallis tests with significance at 2-sided p value < 0.05. Co-culture of PBMCs and pleural effusion-derived tumor cells from individual patients with oncogene-driven NSCLC was used to determine the in vitro cytotoxicity of TKI and ICI.ResultsExcept for low CD3% in cohort A, there were no significant differences in other 12 blood biomarkers among the 3 cohorts at baseline. TKI treatment in cohort A was associated with significant increase in CD3% and decrease in total and absolute neutrophils (p < 0.05). In cohort B, patients with good clinical response to ICI treatment (N = 18) had significant increases in absolute lymphocyte counts (ALCs), CD4 and/or CD8 cell counts. Conversely, those patients with poor clinical response to ICI (N = 17) had significant decreases in these cell counts. Of the 27 patients with pre- and post-treatment blood samples in cohort A, 11 had poor clinical response to TKIs and decreased lymphocyte counts. Of the remaining 16 patients who had good clinical response to TKI therapy, 10 (62.5%) patients had decreased, and 6 (37.5%) patients had increased lymphocyte counts. Multicolor immunophenotyping of PBMCs revealed ICI treatment activated additional immune cell types that need further validation. We confirmed that TKI treatment could either antagonize or enhance the effect of ICIs in the co-culture assay using patient’s tumor cells and PBMCs.ConclusionsTo the best of our knowledge, this is the first study showing that TKIs can have various effects on blood immune cells, which may affect their response to ICIs. Further validation of the blood biomarker and in vitro assay is warranted.

Association of Epstein-Barr virus infection with peripheral immune parameters and clinical outcome in advanced nasopharyngeal carcinoma

The purpose of this study was to investigate the association of Epstein-Barr virus (EBV) with peripheral blood immune cell counts and clinical outcomes in advanced nasopharyngeal carcinoma (NPC) patients. In a retrospective design, 146 patients with NPC at stage IV were enrolled in this study. The association of EBV status with peripheral blood immune cell counts, distant metastases, and long-term survival in patients with advanced NPC were determined. Eighty-seven (59.6%) of all patients were positive for EBV. Compared with patients with normal NK cell count, patients with lower NK cell count showed a significantly lower EBV viral load (median: 614.0 vs. 2190.0 copies/mL, P = 0.024). EBV-positive patients showed a significantly higher incidence of liver metastasis than EBV-negative patients (32.6% vs. 23.7%, P = 0.021). Multi-variant regression analysis showed that EBV infection was independently associated with liver metastasis (OR: 2.33, P = 0.043). EBV positive patients showed a significantly worse PFS (P = 0.001) and OS (P = 0.001) than EBV negative patients. Multivariate Cox regression analysis revealed that EBV infection was independently associated with a worse PFS (HR: 1.94, P = 0.003), and OS (HR: 2.12, P = 0.014) in advanced NPC. In conclusion, EBV infection is associated with a high risk of liver metastasis and is also an independent negative predictor for PFS and OS in patients with advanced NPC. EBV infection is associated with lower CD8% and higher NK%, while lower NK cell count is associated with lower EBV viral load.

Air pollution from traffic during pregnancy impairs newborn's cord blood immune cells: The NELA cohort

BackgroundHazards of traffic-related air pollution (TRAP) on the developing immune system are poorly understood. We sought to investigate the effects of prenatal exposure to TRAP on cord blood immune cell distributions; and to identify gestational windows of susceptibility. MethodsIn-depth immunophenotyping of cord blood leukocyte and lymphocyte subsets was performed by flow cytometry in 190 newborns embedded in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015–2018). Long-term (whole pregnancy and trimesters) and short-term (15-days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2), particulate matter (PM2.5 and PM10), and ozone (O3) were estimated using dispersion/chemical transport modelling. Associations between TRAP concentrations and cord blood immune cell counts were assessed using multivariate Poisson regression models. ResultsMean number of natural killer (NK) cells decreased 15% in relation to higher NO2 concentrations (≥36.4 μg/m3) during whole pregnancy (incidence relative risk (IRR), 0.85; 95% CI, 0.72, 0.99), with stronger associations in the first trimester. Higher PM2.5 concentrations (≥13.3 μg/m3) during whole pregnancy associated with a reduced mean number of cytotoxic T cells (IRR, 0.88; 95% CI, 0.78, 0.99). Newborns exposed to higher PM10 (≥23.6 μg/m3) and PM2.5 concentrations during the first and third trimester showed greater mean number of helper T type 1 (Th1) cells (P < 0.05). Decreased number of regulatory T (Treg) cells was associated with greater short-term NO2 (IRR, 0.90; 95% CI, 0.80, 1.01) and PM10 (IRR, 0.88; 95% CI, 0.77, 0.99) concentrations. ConclusionsPrenatal exposure to TRAP, particularly in early and late gestation, impairs fetal immune system development through disturbances in cord blood leukocyte and lymphocyte distributions.

Schistosoma haematobium infection is associated with lower serum cholesterol levels and improved lipid profile in overweight/obese individuals.

Infection with parasitic helminths has been reported to improve insulin sensitivity and glucose homeostasis, lowering the risk for type 2 diabetes. However, little is known about its impact on whole-body lipid homeostasis, especially in obese individuals. For this purpose, a cross-sectional study was carried out in lean and overweight/obese adults residing in the Lambaréné region of Gabon, an area endemic for Schistosoma haematobium. Helminth infection status, peripheral blood immune cell counts, and serum metabolic and lipid/lipoprotein levels were analyzed. We found that urine S. haematobium egg-positive individuals exhibited lower serum total cholesterol (TC; 4.42 vs 4.01 mmol/L, adjusted mean difference [95%CI] -0.30 [-0.68,-0.06]; P = 0.109), high-density lipoprotein (HDL)-C (1.44 vs 1.12 mmol/L, -0.24 [-0.43,-0.06]; P = 0.009) and triglyceride (TG; 0.93 vs 0.72 mmol/L, -0.20 [-0.39,-0.03]; P = 0.022) levels than egg-negative individuals. However, when stratified according to body mass index, these effects were only observed in overweight/obese infected individuals. Similarly, significant negative correlations between the intensity of infection, assessed by serum circulating anodic antigen (CAA) concentrations, and TC (r = -0.555; P<0.001), HDL-C (r = -0.327; P = 0.068), LDL-C (r = -0.396; P = 0.025) and TG (r = -0.381; P = 0.032) levels were found in overweight/obese individuals but not in lean subjects. Quantitative lipidomic analysis showed that circulating levels of some lipid species associated with cholesterol-rich lipoprotein particles were also significantly reduced in overweight/obese infected individuals in an intensity-dependent manner. In conclusion, we reported that infection with S. haematobium is associated with improved lipid profile in overweight/obese individuals, a feature that might contribute reducing the risk of cardiometabolic diseases in such population.

Characterization of Blood Surrogate Immune-Methylation Biomarkers for Immune Cell Infiltration in Chronic Inflammaging Disorders.

Alzheimer’s disease (AD) and atherosclerosis are both chronic age- and inflammation-dependent diseases. In addition, atherosclerosis is frequently observed in AD patients indicating common involvement of vascular components in both disease etiologies. Recently, epigenome-wide association studies have identified epigenetic alterations, and in particularly DNA methylation changes for both disorders. We hypothesized the existence of a common DNA methylation profile in atherosclerosis and AD which may be valuable as a blood-based DNA methylation inflammaging biomarker. Using publicly available 450k Illumina methylation datasets, we identified a co-methylation network associated with both atherosclerosis and AD in whole blood samples. This methylation profile appeared to indicate shifts in blood immune cell type distribution. Remarkably, similar methylation changes were also detected in disease tissues, including AD brain tissues, atherosclerotic plaques, and tumors and were found to correlate with immune cell infiltration. In addition, this immune-related methylation profile could also be detected in other inflammaging diseases, including Parkinson’s disease and obesity, but not in multiple sclerosis, schizophrenia, and osteoporosis. In conclusion, we identified a blood-based immune-related DNA methylation signature in multiple inflammaging diseases associated with changes in blood immune cell counts and predictive for immune cell infiltration in diseased tissues. In addition to epigenetic clock measurements, this immune-methylation signature may become a valuable blood-based biomarker to prevent chronic inflammatory disease development or monitor lifestyle intervention strategies which promote healthy aging.

Response of cord blood cells to environmental, hereditary and perinatal factors: A prospective birth cohort study

BackgroundMany studies investigating the impact of individual risk factors on cord blood immune cell counts may be biased given that cord blood composition is influenced by a multitude of factors. The aim of this study was to comprehensively investigate the relative impact of environmental, hereditary and perinatal factors on cord blood cells.MethodsIn 295 neonates from the prospective Basel-Bern Infant Lung Development Cohort, we performed complete blood counts and fluorescence-activated cell sorting scans of umbilical cord blood. The associations between risk factors and cord blood cells were assessed using multivariable linear regressions.ResultsThe multivariable regression analysis showed that an increase per 10μg/m3 of the average nitrogen dioxide 14 days before birth was associated with a decrease in leukocyte (6.7%, 95% CI:-12.1,-1.0) and monocyte counts (11.6%, 95% CI:-19.6,-2.8). Maternal smoking during pregnancy was associated with significantly lower cord blood cell counts in multiple cell populations. Moreover, we observed sex differences regarding eosinophilic granulocytes and plasmacytoid dendritic cells. Finally, significantly increased numbers of cord blood cells were observed in infants exposed to perinatal stress. Cesarean section seems to play a significant role in Th1/Th2 balance.ConclusionsOur results suggest that all three: environmental, hereditary and perinatal factors play a significant role in the composition of cord blood cells at birth, and it is important to adjust for all of these factors in cord blood studies. In particular, perinatal circumstances seem to influence immune balance, which could have far reaching consequences in the development of immune mediated diseases.

Immunological effects of behavioral activation with exercise in major depression: an exploratory randomized controlled trial

Major depression (MD) is associated with peripheral inflammation and increased cardiovascular risk. Regular physical exercise can have anti-inflammatory effects. The present study examined whether behavioral activation with exercise affects inflammatory processes in MD. Ninety-eight patients with MD were randomly assigned to cognitive-behavioral therapy (CBT) emphasizing exercise during behavioral activation (CBT-E), CBT with pleasurable low-energy activities as an active control condition (CBT-C) or a passive waiting list control group (WL). Plasma levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, lipopolysaccharide (LPS)-stimulated IL-6 production, and blood immune cell counts were analyzed at baseline and weeks 8 (post-behavioral activation) and 16 (post-treatment). Thirty non-depressed age- and sex-matched controls were included to examine potential immunological alterations in MD at baseline. Patients with MD exhibited higher levels of CRP, higher neutrophil and monocyte counts, lower IL-10 levels and reduced LPS-stimulated IL-6 production compared to controls (P<0.001−0.045). Multilevel modeling indicated that CBT-E was associated with increased anti-inflammatory IL-10 at weeks 8 and 16 compared to CBT-C and WL (P=0.004−0.018). CBT-E did not significantly affect other immunological makers in the total sample. A subgroup analysis including patients with potentially higher cardiovascular risk (CRP ⩾1 μg ml−1) indicated that CRP was reduced in CBT-E compared to CBT-C (P<0.007) and marginally reduced compared to WL (P<0.085) after week 16. The present findings provide new insights into immunological effects of behavioral treatments against depression. Behavioral activation in conjunction with exercise may have the potential to reverse, in part, immunological alterations in MD.

Low Blood Absolute CD4 Counts Is Associated with Inferior Progression Free Survival in Diffuse Large B-Cell Lymphoma Independent of Age and IPI

Tumor-infiltrating immune cells influence diffuse large B-cell lymphoma (DLBCL) outcome. Relatively little is known about the significance of peripheral blood immune cell counts (obtained by generally available flow cytometry) on DLBCL behaviorPatients and methods: 45 newly diagnosed DLBCL patients enrolled in an institutional protocol had blood pretreatment multicolor flow cytometry performed and immune cell counts recorded. The M/F ratio was 24/21, age 19-88, median 64; stage I: 11, II: 13, III: 6 and IV: 15. Thirty two had low/ intermediate International Prognostic Index (IPI) score (0-2) and 13 had 3+ IPI. One patient was HIV+. Thirty seven (82%) received immuno-chemotherapy and 8 had chemotherapy and/or irradiation.Statistical Methods: The outcomes of the study were progression free survival (PFS) and overall survival (OS). Kaplan-Meier estimation method and Log-rank test were used in the univariate analysis. The Cox proportional hazard model was used for multivariable analysis (MVA). All analyses were done via SAS 9.2.Results: Mean absolute CD4 cell count (ACD4C) was 450/c.mm and the median about 400. After follow up of 0.8 to 152 months (median: 73), 25 (56%) were still alive.Univariate analysis: significant predictors to PFS were: age (HR=1.05, 95%CI: 1.02-1.09, p=0.005), ACD4C (HR= 0.998, 95% CI: 0.966-1.000, p= 0.023] and IPI (HR=0.05, 95%CI: 0.995-1.89, p= 0.054). But for OS ACD4C was only marginally significant (p= 0.083). Absolute lymphocyte count (ALC), CD8 and [CD3-C56+ (NK)] counts did not correlate with OS or PFS.When analyzed as a binary variable with cutoff of 450/cmm, the 18 patients with high ACD4C had better 5 year PFS, 88% vs. 52% (p= 0. 023), figure (1), and OS, 88% vs. 59% (0.054) than the 27 with low ACD4C. Age, IPI groups (low /intermediate versus high) and ALC also correlated with PFS and OS, but not the CD8 or NK cell counts.MVA with age as a continuous variable, IPI groups and ACD4C of 450/cmm; age and ACD4C only were significant for PFS, (p= 0.008 and 0.036 respectively). For OS age was the only significant variable (p=0.017). ALC, CD8 and NK cell counts did not correlate with PFS or OS.Conclusion: Though the series contains more early stage patients than usual, blood ACD4C seems to be a predictor of PFS and to a lesser extent OS in DLBCL independent of age and IPI. If confirmed in a larger prospective study of uniformly treated patients ACD4C may serve as an immunological marker for DLBCL biological behavior. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Exercise immunology: nutritional countermeasures.

In contrast to moderate physical activity, prolonged and intensive exertion causes numerous changes in immunity that reflect physiologic stress and suppression, and an increased risk of upper respiratory tract infection. Enzymes in immune cells require the presence of micronutrients, leading to attempts by investigators to alter changes in immunity following heavy exertion through use of nutritional supplements, primarily zinc, dietary fat, vitamin C and other antioxidants, glutamine, and carbohydrate. Except for carbohydrate supplementation, none of these nutrients has emerged as an effective countermeasure to exercise-induced immunosuppression. Data from several studies of endurance athletes suggest that carbohydrate compared to placebo ingestion is associated with an attenuated cortisol, growth hormone, and epinephrine response to heavy exertion, fewer perturbations in blood immune cell counts, lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro- and anti-inflammatory cytokine response. Overall, the hormonal and immune responses to carbohydrate compared to placebo ingestion during intensive exercise suggest that physiologic stress and inflammation are diminished, although clinical significance awaits further research.

NUTRITION, EXERCISE, AND IMMUNE SYSTEM FUNCTION

Many components of the immune system exhibit adverse change after prolonged, intense exertion. During this "open window" of impaired immunity (which may last 3-72 h, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk for subclinical and clinical infection. The influence of nutritional supplements, primarily zinc, vitamin C, glutamine, and carbohydrate, on the acute immune response to prolonged exercise has been measured in endurance athletes. Vitamin C and glutamine have received much attention, but the data thus far are inconclusive. The most impressive results have been reported with carbohydrate supplementation. Carbohydrate beverage ingestion has been associated with increased plasma glucose levels, an attenuated cortisol and growth hormone response, fewer perturbations in blood immune cell counts, decreased granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro-inflammatory and anti-inflammatory cytokine response. Overall these data indicate that the physiologic stress to the immune system is reduced when endurance athletes use carbohydrate beverages before, during, and after prolonged and intense exertion. The clinical significance of these carbohydrate-induced effects on the endocrine and immune systems awaits further research.