scholarly journals Peripheral NF-κB dysregulation in people with schizophrenia drives inflammation: putative anti-inflammatory functions of NF-κB kinases

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Caitlin E. Murphy ◽  
Adam K. Walker ◽  
Maryanne O’Donnell ◽  
Cherrie Galletly ◽  
Andrew R. Lloyd ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Inflammatory Cytokine ◽  
Psychiatric Symptoms ◽  
Inflammatory Factors ◽  
Blood Leukocytes ◽  
Reactive Protein ◽  
Control Subjects ◽  
Inflammatory Status ◽  
Activating Receptors ◽  
Healthy Control

AbstractElevations in plasma levels of pro-inflammatory cytokines and C-reactive protein (CRP) in patient blood have been associated with impairments in cognitive abilities and more severe psychiatric symptoms in people with schizophrenia. The transcription factor nuclear factor kappa B (NF-κB) regulates the gene expression of pro-inflammatory factors whose protein products trigger CRP release. NF-κB activation pathway mRNAs are increased in the brain in schizophrenia and are strongly related to neuroinflammation. Thus, it is likely that this central immune regulator is also dysregulated in the blood and associated with cytokine and CRP levels. We measured levels of six pro-inflammatory cytokine mRNAs and 18 mRNAs encoding NF-κB pathway members in peripheral blood leukocytes from 87 people with schizophrenia and 83 healthy control subjects. We then assessed the relationships between the alterations in NF-κB pathway genes, pro-inflammatory cytokine and CRP levels, psychiatric symptoms and cognition in people with schizophrenia. IL-1β and IFN-γ mRNAs were increased in patients compared to controls (both p < 0.001), while IL-6, IL-8, IL-18, and TNF-α mRNAs did not differ. Recursive two-step cluster analysis revealed that high levels of IL-1β mRNA and high levels of plasma CRP defined ‘high inflammation’ individuals in our cohort, and a higher proportion of people with schizophrenia were identified as displaying ‘high inflammation’ compared to controls using this method (p = 0.03). Overall, leukocyte expression of the NF-κB-activating receptors, TLR4 and TNFR2, and the NF-κB subunit, RelB, was increased in people with schizophrenia compared to healthy control subjects (all p < 0.01), while NF-κB-inducing kinase mRNAs IKKβ and NIK were downregulated in patients (all p < 0.05). We found that elevations in TLR4 and RelB appear more related to inflammatory status than to a diagnosis of schizophrenia, but changes in TNFR2 occur in both the high and low inflammation patients (but were exaggerated in high inflammation patients). Further, decreased leukocyte expression of IKKβ and NIK mRNAs was unique to high inflammation patients, which may represent schizophrenia-specific dysregulation of NF-κB that gives rise to peripheral inflammation in a subset of patients.

scholarly journals The Modulatory Effect of Gender and Cytomegalovirus-Seropositivity on Circulating Inflammatory Factors and Cognitive Performance in Elderly Individuals

2019 ◽  
Vol 20 (4) ◽  
pp. 990 ◽  
Author(s):  
Svetlana Di Benedetto ◽  
Marcel Gaetjen ◽  
Ludmila Müller
Keyword(s):  
Cognitive Performance ◽  
Cognitive Abilities ◽  
Fluid Intelligence ◽  
Inflammatory Factors ◽  
Metabolic Markers ◽  
Inflammatory Status ◽  
Age Related ◽  
Potential Contributor ◽  
Anti Inflammatory ◽  
And Gender

Aging is characterized by a chronic increase in the systemic levels of inflammatory cytokines even in ostensibly healthy individuals. The drivers of age-related increase in systemic inflammation are unclear but one potential contributor may be a persistent infection with Cytomegalovirus (CMV). In this study, we characterized the inflammatory status of 161 older participants recruited to undergo a six-month training intervention. We investigated the influence of gender and CMV-seropositivity on the main inflammatory and anti-inflammatory circulating biomarkers, such as cytokines, receptor antagonist, soluble receptor, immune cells, and relevant metabolic markers. We found that both gender and CMV-seropositivity modulate circulating peripheral biomarkers, and that CMV-infection modifies associations among the latter. Moreover, we observed an interaction between CMV-serostatus and gender associations with cognitive abilities: gender differences in fluid intelligence (Gf) and working memory (WM) were noted only in CMV-negative individuals. Finally, we found that in the CMV-seronegative participants Gf, episodic memory (EM), and WM correlated negatively with pro-inflammatory tumor necrosis factor (TNF); and EM correlated positively with anti-inflammatory interleukin (IL)-10. In CMV-seropositive individuals EM and Gf correlated negatively with pro-inflammatory IL-6, while EM, Gf, and WM correlated negatively with anti-inflammatory IL-1RA. We conclude that both CMV-serostatus and gender may modulate neuroimmune factors, cognitive performance and the relationship between the two domains and should therefore be considered in comparative and interventional studies with elderly people.

scholarly journals The prognosis of functional limb weakness: a 14-year case-control study

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 2137-2148 ◽  
Author(s):  
Jeannette M Gelauff ◽  
Alan Carson ◽  
Lea Ludwig ◽  
Marina A J Tijssen ◽  
Jon Stone
Keyword(s):  
Psychiatric Symptoms ◽  
Illness Perception ◽  
Control Group ◽  
Motor Disorder ◽  
Limb Weakness ◽  
Control Subjects ◽  
Healthy Control ◽  
Baseline Factors ◽  
Functional Limb

Abstract Reliable data on the prognosis of functional motor disorder are scarce, as existing studies of the prognosis of functional motor disorder are nearly all retrospective, small and uncontrolled. In this study we used a prospectively recruited, controlled cohort design to assess misdiagnosis, mortality and symptomatic and health outcome in patients with functional limb weakness compared to neurological disease and healthy control subjects. We also carried out an exploratory analysis for baseline factors predicting outcome. One hundred and seven patients with functional limb weakness, 46 neurological and 38 healthy control subjects from our previously studied prospective cohort were traced for follow-up after an average of 14 years. Misdiagnosis was determined in a consensus meeting using information from records, patients and their GPs. Numbers and causes of death were collected via death certificates. Outcome of limb weakness, physical and psychiatric symptoms, disability/quality of life and illness perception were recorded with self-rated questionnaires. Outcome measures were compared within and between groups. Seventy-six patients (71%) with functional limb weakness, 31 (67%) neurological and 23 (61%) healthy controls were included in follow-up. Misdiagnosis was found in one patient in the functional limb weakness group (1%) and in one neurological control (2%). Eleven patients with functional limb weakness, eight neurological control subjects and one healthy control subject had died. Weakness had completely remitted in 20% of patients in the functional limb weakness group and in 18% of the neurological controls (P = 0.785) and improved in a larger proportion of functional limb weakness patients (P = 0.011). Outcomes were comparable between patient groups, and worse than the healthy control group. No baseline factors were independent predictors of outcome, although somatization disorder, general health, pain and total symptoms at baseline were univariably correlated to outcome. This study is the largest and longest follow-up study of functional limb weakness. Misdiagnosis in functional limb weakness is rare after long-term follow-up. The disorder is associated with a higher mortality rate than expected, and symptoms are persistent and disabling. It appears difficult to predict outcome based on common baseline variables. These data should help inform clinicians to provide a more realistic outlook of the outcome and emphasize the importance of active and targeted therapy.

scholarly journals The Serum High-Sensitive C Reactive Protein and Homocysteine Levels to Evaluate the Prognosis of Acute Ischemic Stroke

2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Tahir Yoldas ◽  
Murat Gonen ◽  
Ahmet Godekmerdan ◽  
Fulya Ilhan ◽  
Ednan Bayram
Keyword(s):  
Ischemic Stroke ◽  
Clinical Status ◽  
Elevated Serum ◽  
Short Term ◽  
Reactive Protein ◽  
Control Subjects ◽  
Common Causes ◽  
Healthy Control ◽  
The Mean ◽  
The Relationship

Ischemic stroke is one of the most common causes of death worldwide and is most often caused by thrombotic processes. We investigated the changes in hsCRP and homocysteine levels, two of these risk factors, during the acute period of ischemic stroke and evaluated the relationship between these levels and the short-term prognosis. HsCRP and homocysteine levels were measured at the 2nd, 5th, and 10th days in forty patients admitted within second of an ischemic stroke. The clinical status of the patients was simultaneously evaluated with the Scandinavian stroke scale. The results were compared with 40 healthy control subjects whose age and sex were matched with the patients. The mean hsCRP levels of the patients were9.4±7.0mg/L on the 2nd day,11.0±7.4mg/L on the 5th day, and9.2±7.0mg/L on the 10th day. The mean hsCRP level of the control subjects was1.7±2.9mg/L. The mean hsCRP levels of the patients on the 2nd, 5th, and 10th days were significantly higher than the control subjects (P<.001). The patients' mean homocysteine levels were40.6±9.6μmol/L on the 2nd day,21.7±11.1μmol/L on the 5th day, and20.7±9.2μmol/L on the 10th day. The mean homocysteine level of the control subjects was11.2±1.1μmol/L. The homocysteine levels of the patients were higher than the control subjects at all times (P<.01). In conclusion, patients with stroke have a higher circulating serum hsCRP and homocysteine levels. Short-term unfavorable prognosis seems to be associated with elevated serum hsCRP levels in patients with stroke. Although serum homocysteine was found to be higher, homocysteine seems not related to prog nosis.

scholarly journals Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington’s Disease Patients and Healthy Control Subjects

2020 ◽  
Vol 21 (17) ◽  
pp. 6363 ◽  
Author(s):  
Jody Corey-Bloom ◽  
Ryan S. Fischer ◽  
Aeri Kim ◽  
Chase Snell ◽  
Georgia M. Parkin ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Neurodegenerative Disorder ◽  
Interleukin 1 ◽  
Peripheral Tissues ◽  
Reactive Protein ◽  
Control Subjects ◽  
Healthy Control

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.

Myeloperoxidase (MPO) and Interleukin-17 (IL-17) Plasma Levels are Increased in Patients with Acute Coronary Syndromes

2009 ◽  
Vol 37 (3) ◽  
pp. 862-866 ◽  
Author(s):  
J Liang ◽  
Z Zheng ◽  
M Wang ◽  
L Han ◽  
Z Zheng ◽  
...  
Keyword(s):  
Stable Angina ◽  
Acute Coronary Syndromes ◽  
Inflammatory Cytokine ◽  
Interleukin 17 ◽  
Data Set ◽  
Control Subjects ◽  
Healthy Control ◽  
Coronary Syndromes ◽  
Study Participants ◽  
Age And Sex

There are several reports of myeloperoxidase (MPO) playing an important role in acute coronary syndromes (ACS). Interleukin-17 (IL-17) is a pro-inflammatory cytokine produced by activated CD4 T cells that has a chemotactic and activating effect on neutrophils. It has also been shown that IL-17 recruits neutrophils via the release of C-X-C chemokines. The roles of MPO and IL-17 in ACS, however, have not been established. This study measured plasma MPO and IL-17 levels in 10 patients with ACS, 11 age- and sex-matched patients with stable angina and 12 healthy control subjects. Plasma MPO and IL-17 levels were significantly elevated in ACS patients compared with the patients with stable angina and the healthy control subjects. In addition, plasma MPO levels correlated with plasma IL-17 levels in all study participants. It is concluded that MPO and IL-17 are powerful indicators of acute coronary inflammation, however the data set was very small, so larger prospective studies are required.

Hopelessness and Psychiatric Symptomatology in Hospitalized Physically Ill Adolescents

1996 ◽  
Vol 26 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Anthony L. Pillay ◽  
Douglas R. Wassenaar
Keyword(s):  
Psychiatric Symptoms ◽  
The Other ◽  
Psychiatric Disturbance ◽  
Psychiatric Symptomatology ◽  
Healthy Group ◽  
Matched Group ◽  
Control Subjects ◽  
Healthy Control ◽  
The One

This study compares scores on psychiatric disturbance and hopelessness in two adolescent samples. The one sample was a physically ill hospitalized group, and the other was a matched group of healthy control subjects. It was found that the hospitalized physically ill group scored significantly higher on both psychiatric disturbance and hopelessness than the healthy group. At six-month follow-up, the physically ill group's scores on psychiatric disturbance had declined significantly, but hopelessness scores remained significantly high. In line with other findings, this study suggests that insufficient clinical attention is paid to psychiatric symptoms in hospitalized physically ill patients, and that the high hopelessness scores after six months warrant clinical psychological evaluation.

scholarly journals Vitamin D in acutely ill patients

2018 ◽  
Vol 46 (10) ◽  
pp. 4246-4257 ◽  
Author(s):  
Ifigenia Kostoglou-Athanassiou ◽  
Eleni Pantazi ◽  
Sofoklis Kontogiannis ◽  
Dimitrios Kousouris ◽  
Iordanis Mavropoulos ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Inverse Relationship ◽  
Control Group ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Control Subjects ◽  
Healthy Control ◽  
The Mean

Objective To investigate 25(OH)D3 levels and their relationship to survival in a cohort of acutely ill patients on admission to an intensive care unit. Methods This study enrolled acutely ill patients at admission to an intensive care unit and a group of sex- and age-matched healthy control subjects. The 25(OH)D3 levels were measured using an enzyme immunoassay. C-reactive protein and procalcitonin levels were also measured using immunoassays. Results A total of 50 acutely ill patients and 50 healthy control subjects were enrolled in the study. The mean ± SEM 25(OH)D3 levels were significantly lower in the acutely ill patients compared with the control group (11.74 ± 0.88 ng/ml versus 24.66 ± 1.60 ng/ml, respectively). The 25(OH)D3 levels were not related to survival. An inverse relationship was observed between 25(OH)D3 levels and C-reactive protein levels. A weak inverse relationship was also observed between 25(OH)D3 levels and procalcitonin levels. Conclusions The 25(OH)D3 levels were decreased in acutely ill patients admitted to an intensive care unit compared with healthy control subjects. 25(OH)D3 levels may be inversely related to C-reactive protein and procalcitonin levels.

scholarly journals Evaluation of Inflammatory State in Migraineurs: A Case-control Study

2020 ◽  
Author(s):  
Mansoureh Togha ◽  
Soodeh Razeghi Jahromi ◽  
Zeinab Ghorbani ◽  
Amir Ghaemi ◽  
Pegah Rafiee
Keyword(s):  
Demographic Data ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Reactive Protein ◽  
Tnf Α ◽  
Inflammatory State ◽  
Healthy Control ◽  
Positive Correlations ◽  
Episodic Migraineurs

Due to inconclusive findings of previous researches, we aimed to evaluate inflammatory state biomarkers in episodic and chronic migraineurs (EM and CM patients) compared to headache-free controls in the current study. Seventy-one migraine patients and 19 age-sex-matched controls were recruited. After obtaining demographic data and recording headache characteristics, blood samples were gathered and analyzed to evaluate the serum levels of C-reactive protein(CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-6. Serum levels of IL-6, CRP and TNF-α were significantly higher among subjects with CM than the EM and controls. Further, positive correlations were noted for number of headache days/month and serum IL-6 (r=0.53, p<0.001), CRP (r=0.62, p<0.001), and TNF-α (r=0.58, p<0.001). In sum, according to current findings, a pro-inflammatory state was detected among chronic and episodic migraineurs compared to healthy control, as revealed by augmented concentrations of pro-inflammatory cytokines (e.g. IL6, CRP, and TNF-α). It was also underlined that with increasing levels of inflammatory factors, headaches tended to be more chronic. However, in order to confirm the hypothesis that neuroinflammation plays a role in migraine pain genesis, long-term cohort studies and well-designed experimental and randomized controlled trials are required.

scholarly journals The Correlation of Serums CCL11, CCL17, CCL26, and CCL27 and Disease Severity in Patients with Urticaria

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Lu ◽  
Xiaoyang Jiao ◽  
Mengya Si ◽  
Ping He ◽  
Jinbo Zou ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthy Controls ◽  
Strongly Correlated ◽  
C Reactive Protein ◽  
Total Ige ◽  
Reactive Protein ◽  
Control Subjects ◽  
Healthy Control ◽  
D Dimer

Background.Chemokines may be involved in the pathogenesis of urticaria, but their correlation with disease severity as well as eruption type is unclear.Objectives.The aim of this study was to explore the expression of chemokines in patients with urticaria. The association between disease severity and levels of chemokines was analysed.Materials and Methods.Serums CCL11, CCL17, CCL26, and CCL27, D-dimer, C-reactive protein, and total IgE were measured in 51 patients with urticaria and in 25 healthy control subjects.Results.Serums CCL11, CCL17, CCL26, and CCL27 were significantly higher in patients with urticaria than in the healthy controls (P<0.05). Serum CCL27 strongly correlated with urticarial disease severity. Serums CCL17, CCL26, and CCL27 significantly correlated with D-dimer, while innercorrelations were noted among the chemokines.Conclusion.Our findings reveal that chemokines participate in the pathogenesis of urticaria. Further study in larger cohort is needed to testify whether they could be the biomarkers for predicting the severity of urticaria.

Enhancement of Platelet Sensitivity to ADP-Aggregation by Isometric Exercise in Arteriosclerotic Patients and its Prevention

1977 ◽  
Vol 37 (02) ◽  
pp. 329-338 ◽  
Author(s):  
Tadahiro Sano ◽  
Takeshi Motomiya ◽  
Hiroh Yamazaki ◽  
Takio Shimamoto
Keyword(s):  
Cyclic Amp ◽  
Mechanical Stress ◽  
Optical Density ◽  
Platelet Function ◽  
Isometric Exercise ◽  
Phosphodiesterase Inhibitor ◽  
New Method ◽  
Platelet Aggregability ◽  
Control Subjects ◽  
Healthy Control

SummaryA new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.3. It was proved to be highly reproducible and is thought to be useful clinically.By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.

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