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)

This review analyses the recent literature devoted to two related fatigue syndromes: chronic fatigue syndrome (CFS) and acute onset postviral fatigue syndrome (PVFS). The articles are grouped into five pathogenic tracks: infectious agents, immune system, skeletic muscle, hypothalamo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a particular infectious agent is unlikely to be responsible for all CFS cases, evidence is shown that host-parasite relationships are modified in a large proportion of patients with chronic fatigue. Antibody titres against infectious agents are often elevated and replication of several viruses could be increased. Chronic activation of the immune system is also observed and could be due to the reactivation of persistent or latent infectious agents such as herpes viruses (i.e. HHV-6) or enteroviruses. It could also be favorised by an impaired negative feedback of the HPA axis on the immune system. A model is proposed where the abnormalities of the HPA axis are primary events and are mainly responsible for a chronic activation of the immune system which in turn induces an increased replication of several viruses under the control of cellular transcription factors. These replicating viruses together with cytokines such as TNF-alpha would secondarily induce functional disorders of muscle and several aspects of asthenia itself.
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PMID:Pathogenic tracks in fatigue syndromes. 787 34

Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha have been proposed to play a role in the pathogenesis of fatigue. In the present study we compared the susceptibility of two mouse strains to immunologically induced fatigue. Daily running of two strains of mice, Balb/c and C57BL/ 6, was assessed after a single injection of Corynebacterium parvum antigen (2 mg/mouse). Spontaneous running activity of each animal was compared to mean running distance prior to injection. To evaluate the involvement of cytokines in fatigue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cytokine mRNA expression was analyzed in the brains of mice at different time periods after immunologic challenge. A significant difference in running activity between the two mice strains was observed after C. parvum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) reduction in running activity (relative to preinjection levels) and slower recovery to baseline than Balb/c mice. Injection of antibodies specific to either IL-1beta or TNF-alpha did not alter immunologically induced fatigue, suggesting a lack of involvement of these cytokines produced outside of the central nervous system (CNS). However, increased TNF-alpha and IL-1beta mRNA expression was found in the brains of C57BL/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C. parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue. These findings are consistent with the hypothesis that expression of proinflammatory cytokines within the CNS plays a role in the pathogenesis of immunologically mediated fatigue.
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PMID:Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice. 890 47

An increasing number of persons say that they get cutaneous problems as well as symptoms from certain internal organs, such as the central nervous system (CNS) and the heart, when being close to electric equipment. A major group of these patients are the users of video display terminals (VDTs), who claim to have subjective and objective skin- and mucosa-related symptoms, such as pain, itch, heat sensation, erythema, papules, and pustules. The CNS symptoms are, e.g. dizziness, tiredness, and headache. Erythema, itch, heat sensation, edema and pain are also common symptoms of sunburn (UV dermatitis). Alterations have been observed in cell populations of the skin of patients suffering from so-called "screen dermatitis" similar to those observed in the skin damaged due to ultraviolet (UV) light or ionizing radiation. In "screen dermatitis" patients a much higher number of mast cells have been observed. It is known that UVB irradiation induces mast cell degranulation and release of TNF-alpha. The high number of mast cells present in the "screen dermatitis" patients and the possible release of specific substances, such as histamine, may explain their clinical symptoms of itch, pain, edema and erythema. The most remarkable change among cutaneous cells, after exposure with the above-mentioned irradiation sources, is the disappearance of the Langerhans' cells. This change has also been observed in "screen dermatitis" patients, again pointing to a common cellular and molecular basis. The results of this literature study demonstrate that highly similar changes exist in the skin of "screen dermatitis" patients, as regards the clinical manifestations as well as alterations in the cell populations, and in skin damaged by UV light or ionizing radiation.
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PMID:Skin changes in "screen dermatitis" versus classical UV- and ionizing irradiation-related damage--similarities and differences. 941 15

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.
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PMID:A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines. 943 Feb 54

The shock syndrome has been classically considered as a consequence of both decreased tissue perfusion and O2 supply; however, in some types of shock like septic or traumatic ones, regional blood flows may be increased. A decade ago, mitochondrial alterations consistent with uncoupling of oxidative phosphorylation were reported in either endotoxemic or hemorrhagic experimental shock or in humans. Recently, the discovery of nitric oxide (NO) and its increase in the shock state, has opened new perspectives in the understanding of this problem. Nitric oxide produces vasodilatation and, at the same time, increases the mitochondrial production of O2 active species like superoxide anion. Both radicals react to form a strong oxidant that is able to nitrate the phenolic rings of proteins: peroxynitrite. This effect leads to the impairment of the activities of different mitochondrial enzymes like succinate dehydrogenase and ATPase and the mitochondrial function and finally, to decreased energy levels and to multiorgan failure. The increase in NO release is due to the effects of circulating peptides and of increased adhesion of neutrophils to the endothelium and to the positive effects of inflammatory mediators like TNF-alpha and cytokines on inducible NOS (iNOS) expression in endothelium and tissues. It is suggested that the shock state is the consequence of an imbalance between NO and O2 and their metabolites.
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PMID:[Shock: concepts for a definition]. 981 94

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well.
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PMID:The role of cytokines in cancer-related fatigue. 1159 87

To investigate whether cytokine responses may have a bearing on the symptoms and outcome of parvovirus B19 infection, circulating cytokines were measured during acute infection (n=51), follow-up of acute infection (n=39) and in normal healthy controls (n=50). At acute B19 virus infection (serum anti-B19 IgM-positive), patients ranged in age from 4 to 54 years, with a mean age of 28.2 years. The male:female ratio was 1:4.1 and symptoms were rash (n=15), arthralgia (n=31), fatigue (n=8), lymphadenopathy (n=4), foetal hydrops (n=3), transient aplastic crisis (n=2), neutropenia (n=2), myelodysplasia (n=1), thrombocytopenia (n=1) and pancytopenia (n=1). Of these patients, 39 were contacted after a follow-up period of 2-37 months (mean of 22.5 months). In comparison with normal controls, detectable IL-6 was associated with acute B19 virus infection (26%; P=0.0003), but not with follow-up (6%; P=0.16). Detection of interferon (IFN)-gamma was associated with acute B19 virus infection (67%; P<0.0001) and follow-up (67%; P<0.0001). Detection of tumour necrosis factor (TNF)-alpha was associated with acute B19 virus infection (49%; P<0.0001) and follow-up (56%; P<0.0001). IL-1beta was detected in acute infection (20%), but not at follow-up. At acute B19 virus infection, detection of serum/plasma IL-6 was associated with rheumatoid factor (P=0.038) and IFN-gamma (> or =7 pg/ml) was associated with fatigue in those patients of > or =15 years of age (P=0.022). At follow-up, fatigue was associated with IFN-gamma (> or =7 pg/ml) and/or TNF-alpha (> or =40 pg/ml) (P=0.0275). Prolonged upregulation of serum IFN-gamma and TNF-alpha appears to represent a consistent host response to symptomatic B19 virus infection.
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PMID:Circulating tumour necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. 1171 78

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.
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PMID:Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. 1200 21

Sleep is an important component of mammalian homeostasis, vital for survival. Sleep disorders are common in the general population and are associated with significant medical, psychologic, and social disturbances. Sleep, in particular deep sleep, has an inhibitory influence on the HPA axis, whereas activation of the HPA axis or administration of glucocorticoids can lead to arousal and sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24-hour increase of ACTH and cortisol secretion, consistent with a disorder of central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in the general population, and recent studies have demonstrated that the proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy, and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime hypersecretion of IL-6. Combined, these findings suggest that the HPA axis stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive daytime sleepiness in humans.
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PMID:Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple interactions and disturbances in sleep disorders. 1205 86

Thalidomide--banned from clinical use in the 1960s because of severe teratogenicity--is now back in clinical practice as an effective agent in the treatment of relapsed and refractory multiple myeloma. Several clinical trials have determined that thalidomide is active in 25-35% of patients with relapsed myeloma. The role of thalidomide in early-stage myeloma is being actively investigated. Thalidomide has antiangiogenic and immunomodulatory properties and is an effective inhibitor of TNF-alpha. However, the mechanism of its action in myeloma remains unclear. Major toxicities of thalidomide include constipation, sedation, skin rash, fatigue and peripheral neuropathy. This paper summarizes the current status of thalidomide in multiple myeloma.
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PMID:Thalidomide in the treatment of multiple myeloma. 1211 24


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