Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer-related fatigue (CRF) is a prevalent and distressing symptom experienced by patients during cancer therapy. One proposed mechanism for the development of fatigue is the increased secretion of proinflammatory cytokines and/or the development of anemia. The major purpose of this pilot study was to investigate the levels of fatigue and cytokines during radiation therapy and determine whether there was a correlation between the two. A secondary purpose was to explore the relationships among hemoglobin values, cytokines, and fatigue. Participants included 15 women diagnosed with uterine cancer, who received curative external radiation therapy. Fatigue was assessed by a self-report instrument (Multidimensional Fatigue Inventory [MFI-20]) and hemoglobin and cytokines (Il-1, Il-6, and TNF-alpha) were measured before, during, and after radiotherapy. The degree of fatigue increased during radiotherapy without a significant change in IL-1, IL-6, or TNF-alpha levels. There was no significant correlation between changes in general fatigue and the changes in IL-1 and TNF-alpha. There was a significant negative correlation between the change in IL-6 and general fatigue. The hemoglobin levels did decrease significantly during radiotherapy, but there was no significant correlation between general fatigue and hemoglobin after 3 weeks of therapy or after the completion of therapy. In conclusion, pelvic radiotherapy in women with uterine cancer is associated with increased fatigue. There were no significant relationships between anemia or cytokine levels and fatigue. The pathogenesis of fatigue during radiation therapy remains to be elucidated.
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PMID:Levels of fatigue compared to levels of cytokines and hemoglobin during pelvic radiotherapy: a pilot study. 1473 21

There is increasing evidence that an ongoing cytokine-induced acute-phase response (sometimes called low-grade inflammation, but part of a widespread activation of the innate immune system) is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis. Elevated circulating inflammatory markers such as C-reactive protein and interleukin-6 predict the development of type 2 diabetes, and several drugs with anti-inflammatory properties lower both acute-phase reactants and glycemia (aspirin and thiazolidinediones) and possibly decrease the risk of developing type 2 diabetes (statins). Among the risk factors for type 2 diabetes, which are also known to be associated with activated innate immunity, are age, inactivity, certain dietary components, smoking, psychological stress, and low birth weight. Activated immunity may be the common antecedent of both type 2 diabetes and atherosclerosis, which probably develop in parallel. Other features of type 2 diabetes, such as fatigue, sleep disturbance, and depression, are likely to be at least partly due to hypercytokinemia and activated innate immunity. Further research is needed to confirm and clarify the role of innate immunity in type 2 diabetes, particularly the extent to which inflammation in type 2 diabetes is a primary abnormality or partly secondary to hyperglycemia, obesity, atherosclerosis, or other common features of the disease.
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PMID:Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. 1498 10

The aim of the study was to characterise the profile and clinical correlates (arthritis, rash, and fatigue) of cytokines, chemokines, and other mediators in symptomatic acute parvovirus B19 infection. Serum was examined from cases of acute B19 infection (as defined by serum anti-B19 IgM positivity) (n = 84), and in normal persons (n = 43) for B19 markers (serum B19 antibodies and DNA), rheumatoid factor (RF), and antinuclear antibody (ANA). A panel of cytokines/chemokines was measured in duplicate using the Bioplex Protein Array system (BioRad Hemel Hempstead, UK). These included interleukin-1 beta (IL-1 beta), IL-4, IL-5, IL-6, IL-8, IL-13, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), macrophage chemoattractant protein-1 (MCP-1), granulocyte-monocyte colony stimulating factor (GM-CSF), transforming growth factor-beta1 (TGF-beta 1), endothelin-1 (ET-1), and neopterin. Acute symptomatic infection was characterised by specific IgG positivity (83%), serum B19 DNA positivity (96%), and raised levels of IL-4, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, GM-CSF, TGF-beta 1, and ET-1. Patients with acute B19-associated arthritis were found to have lower levels of IL-6, TNF-alpha, and GM-CSF than patients without arthritis, while those with rash had lower levels of TGF-beta 1. It is concluded that cytokine levels following acute symptomatic infection with parvovirus B19 indicate a state of immune activation. The profile of circulating mediators may provide insights into the possible pathogenesis of particular clinical manifestations of this infection.
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PMID:Circulating cytokines and chemokines in acute symptomatic parvovirus B19 infection: negative association between levels of pro-inflammatory cytokines and development of B19-associated arthritis. 1525 81

While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.
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PMID:A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. 1531 38

Interferon-alpha is a potent inducer of the cytokine network and is notorious for causing behavioral alterations. Studies on interferon-alpha-treated patients reveal at least two distinct syndromes: 1) a mood/cognitive syndrome that appears late during interferon-alpha therapy is responsive to antidepressants and is associated with activation of neuroendocrine pathways and altered serotonin metabolism; and 2) a neurovegetative syndrome characterized by psychomotor slowing, and fatigue that appears early during interferon-alpha treatment is antidepressant nonresponsive and may be mediated by alterations in basal ganglia dopamine metabolism. Findings from interferon-alpha may provide important clues regarding the pathophysiology and treatment of cytokine-induced behavioral changes in medically ill patients, while also potentially modeling the development of neuropsychiatric symptoms in patients without medical disorders.
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PMID:Cytokines and psychopathology: lessons from interferon-alpha. 1557 57

Anemia is found in about one-third of all cases of congestive heart failure (CHF). The most likely common cause is chronic kidney insufficiency (CKI), which is present in about half of all CHF cases. The CKI is likely to be due to the renal vasoconstriction that often accompanies CHF and can cause long-standing renal ischemia. This reduces the amount of erythropoietin (EPO) produced in the kidney and leads to anemia. However, anemia can occur in CHF without CKI and is likely to be due to excessive cytokine production (for example, tumor necrosis factor-alfa (TNF-alfa) and interleukin-6 (IL-6)), which is common in CHF and can cause reduced EPO secretion, interference with EPO activity in the bone marrow and reduced iron supply to the bone marrow. The anemia itself can worsen cardiac function, both because it causes cardiac stress through tachycardia and increased stroke volume, and because it can cause a reduced renal blood flow and fluid retention, adding further stress to the heart. Long-standing anemia of any cause can cause left ventricular hypertrophy (LVH), which can lead to cardiac cell death through apoptosis and worsen the CHF. Therefore, a vicious circle is set up wherein CHF causes anemia, and the anemia causes more CHF and both damage the kidneys worsening the anemia and the CHF further. We have termed this vicious circle the cardio renal anemia (CRA) syndrome. Patients with CHF who are anemic are often resistant to all CHF medications resulting in being hospitalized repeatedly. Many studies also demonstrate that these patients die more rapidly than their non-anemic counterparts do. In addition, they have a more rapid deterioration in their renal function and can end up on dialysis. There is now evidence from both uncontrolled and controlled studies that early correction of the CHF anemia with subcutaneous EPO and intravenous (i.v.) iron improves shortness of breath and fatigue, cardiac function, renal function and exercise capability, dramatically reducing the need for hospitalization. For these reasons, it is not surprising that quality of life has also been shown to improve. As both CHF and end-stage renal disease (ESRD) are rapidly increasing, the possibility that these twin conditions can be improved by the adequate treatment of anemia offers new hope for slowing the progression of both conditions.
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PMID:The role of anemia in the progression of congestive heart failure. Is there a place for erythropoietin and intravenous iron? 1559 47

Chronic fatigue sindrome is a relatively unknown and underdiagnosed entity in Italy where its epidemiology remains uncertain, as well as its etiology, although it causes important disability in those affected. Classification criteria by Fukuda are available to diagnose the syndrome. Its epidemiology indicates that it is probably more frequent in Northern countries and it is described in Gulf War veterans. Etiological hypotheses include infectious diseases, immunology and neurology. Among these hypotheses sickness behavior mimes certain aspects of this syndrome and is characterized by a cytokine imbalance in the central nervous system and in the periphery. There are no valid therapies available at the moment. In the laboratory of Immunogenetics, we are constituting a biological bank of the syndrome to study the immunogenetic aspects of the disease in the hope of delucidating some of the obscure areas of its etiopathogenesis.
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PMID:[Chronic fatigue syndrome: a review]. 1559 93

Recombinant preparations of the cytokine interferon (IFN)-alpha are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFN alpha induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFN alpha, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFN alpha-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21-58% of patients receiving IFN alpha, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFN alpha dosage and treatment duration. The available data support two approaches to the pharmacological management of IFN alpha-induced depression: antidepressant pretreatment or symptomatic treatment once IFN alpha has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFN alpha-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFN alpha-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFN alpha appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFN alpha and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabilizer should be initiated.
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PMID:Neuropsychiatric adverse effects of interferon-alpha: recognition and management. 1569 25

A phase 1 study was conducted to assess the safety and immunologic response induced by direct injection of autologous immature dendritic cells (DCs) into tumor under radiotherapy in advanced hepatoma patients. Patients with advanced/metastatic stage hepatoma not suitable for surgery or transarterial embolization were enrolled. Groups of patients received two vaccinations. Each vaccination consisted of intratumoral injections of autologous immature DCs in four dose cohorts of 5 x 10(6), 1.5 x 10(7), 3 x 10(7), and 5 x 10(7) cells 2 days after a single fraction of conformal radiotherapy of 8 Gy. The second vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed two cycles of vaccination. The treatment was well tolerated at any of the dose levels. Six patients had mild transient fever (grade 1-2) with chill reactions, three patients developed grade 1 fatigue, and one patient developed mild myalgia and arthralgia after DC injections. There was no evidence of clinically manifested autoimmune disease. There were two partial responses and four minor responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was found in three patients. Ten patients had completed immunologic response evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune response was evident in eight patients examined by cytokine release assay and in seven patients by ELISPOT assay. Six patients showed an increased NK cell cytotoxic activity after vaccination. These data suggest that the combination of intratumoral injection of DCs and conformal radiotherapy is safe and can induce tumor-specific and innate immunity.
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PMID:Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. 1572 56

This study intended to examine if the immune response to a cognitive task as a variant of psychological stress in MS patients is distinct from healthy controls. The experiment was part of a larger study on mechanisms and measurements of MS fatigue. Patients (n =23) and controls (n =25) participated in a cognitive task lasting 40 minutes, in which the heart rate was continuously monitored. Blood samples were taken at baseline and directly after the stress-inducing task Whole blood stimulated cytokine production representative of the TH-1 (i.e. IFNgamma, TNFalpha) and TH-2 paradigm (i.e. IL-10) was evaluated in relation to disability, fatigue, cognitive deficit, and anxiety. Patients scored high on a disease specific fatigue score compared to controls, whereas baseline cytokine patterns did not differ between the groups. MS patients displayed a blunted response of IFNgamma (P =0.03) whereas TNFalpha and IL-10 responses did not change. Additionally MS patients showed a significantly lower heart rate increase after the task (P <0.001). Cognitive impairment was associated with a decreased heart rate reactivity (P =0.02) while depressive symptoms correlated with stronger IL-10 responses (P =0.05). Overall, cognitive stress induces IFNgamma production in healthy controls but not in MS patients with fatigue. Furthermore, a reduced cardiac response might indicate an autonomic dysfunction in this group of patients.
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PMID:Altered cytokine responses to cognitive stress in multiple sclerosis patients with fatigue. 1573 67


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