UMLS:C0015672 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0015672 (fatigue)
51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels.APA levels were determined on serum samples by an indirect ELISA kit that detects IgG APA. Cytokines (IL-1, IL-6, IL-8, IL-10 and TNFalpha) were measured by ELISA in plasma. The impact of FM on the quality of life was estimated using the Fibromyalgia Impact Questionnaire, while pain severity was evaluated using a visual analogic scale. Patients were also characterized by the presence of tiredness, stiffness, nonrestorative sleep, anxiety, depression, tension headache, irritable bowel syndrome, temporomandibular dysfunction and Raynaud's phenomena. Using a cut-off value of 30 U, APA-positive values were detected in 60 FM patients (21.05%) and in 15 healthy control individuals (15.00%) without significant differences among their levels or the percentage of seropositivity. FM patients with moderate and severe symptoms had slightly higher APA levels with respect to patients with mild symptoms. APA-seropositive patients exhibited significant correlations between APA levels and the Fibromyalgia Impact Questionnaire estimate (P = 0.042), tiredness (P = 0.003) and IL-1 levels (P = 0.0072). In conclusion, APA cannot be considered a marker of disease in Italian FM patients. The presence of APA, however, might permit the identification of a subset of FM patients with more severe symptoms and of patients who may respond differently to different therapeutic strategies.
...
PMID:Antipolymer antibody in Italian fibromyalgic patients. 1782 28

Fatigue without coincident depression may accompany many neurological disorders, including multiple sclerosis, Parkinson's disease, motor neuron disease, stroke and post-polio syndrome, and is frequently reported by patients as a predominant complaint. The pathophysiology of fatigue is unknown. The role of various mechanisms has been suggested, including the effect of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) on glutaminergic transmission, hypothalamo-pituitary-adrenal (HPA) axis dysfunction, disturbances of astroglia metabolism and decreased levels of the neurotransmitters noradrenaline and serotonin. The diagnosis of fatigue syndrome is based on exclusion of depression and additional organic conditions (anaemia, cardiovascular disorders, kidney diseases or hypothyroidism). The treatment of fatigue syndrome is complex. Physical activity, rehabilitation, psychotherapy and avoidance of factors which may increase fatigue, such as fever, anxiety, depression, pain, sleep disturbances, as well as some drugs like opioids and benzodiazepines, are important. Pharmacological treatment leads to slight improvement. Amantadine, modafinil and pemoline are administered to such patients.
...
PMID:[Fatigue syndrome in chronic neurological disorders]. 1787 43

Interleukin (IL)-6 cDNA was originally cloned as a terminal B cell differentiation factor into antibody-producing plasma cells. This revealed that it is a multifunctional cytokine that acts on a variety of cells. From the clinical viewpoint, it is especially important that IL-6 acts on hepatocytes to induce acute-phase reactants, including C-reactive protein, serum amyloid A protein, and fibrinogen, and to decrease serum albumin levels. Very recently, this cytokine has been found to enhance the synthesis of a peptide called hepcidin in the liver which regulates iron recycling, resulting in anemia due to hypofferemia. It has also been shown that IL-6 is responsible for various clinical symptoms, including the appearance of autoantibodies, fatigue, anemia, anorexia, fever, and increases in the erythrocyte sedimentation rate, all of which develop in patients with various chronic autoimmune inflammatory diseases. In practice, blocking the IL-6 signaling pathway with a recombinant humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), has dramatically improved all the signs and symptoms of these patients. A study in mice demonstrated that IL-6 promotes the development of a new type of T-helper cells called Th17 cells that impact the pathogenesis of autoimmune diseases. This suggests that TCZ is not only an antiinflammatory agent but also might affect basic autoimmunity. In this review, recent advances in the immunobiology of interleukin-6 related to immune-mediated diseases are discussed.
...
PMID:Recent advances in immunopathophysiology of interleukin-6: an innovative therapeutic drug, tocilizumab (recombinant humanized anti-human interleukin-6 receptor antibody), unveils the mysterious etiology of immune-mediated inflammatory diseases. 1797 66

Twenty-four Angus x Hereford crossbred steers (247 kg BW; SE = 2.4 kg) were used in a completely random design to evaluate the effect of energy source and level with or without antibiotic administration on measures of immune function. Steers were fed 1 of 3 dietary treatments: a 70% concentrate diet ad libitum (70AL), a 30% concentrate diet ad libitum (30AL), and a 70% concentrate diet offered in an amount calculated to provide NE(g) intake equal to the 30AL treatment (70RES). Half the steers in each dietary treatment received a s.c. injection of tilmicosin phosphate (ANTI; 1 mL/30 kg of BW); the other half received an equal volume of saline s.c. (SAL). Steers were offered the treatment diets for 28 d before and were administered the ANTI or SAL injections 2 d before indwelling catheters were placed in the jugular vein and 2.0 microg/kg of BW of Escherichia coli lipopolysaccharide (LPS) was administered i.v. Blood serum was collected at 30-min intervals from -2 to 6 h and at 8, 12, 24, 48, and 72 h relative to the LPS challenge. Increased energy intake (70AL) increased (P < or = 0.04) DMI, ADG, and rectal temperature (RT) after the challenge compared with the 70RES treatment. The 30AL treatment increased the maximum concentrations and area under the response curve of the proinflammatory cytokines (PIC) interferon-gamma, tumor necrosis factor-alpha, and IL-6 (P < or = 0.05) compared with the average of the 70AL and 70RES treatments. Decreased energy intake (70RES vs. 70AL) increased IL-6 (P < or = 0.003) but did not significantly increase interferon-gamma and tumor necrosis factor-alpha (P > or = 0.14) after LPS administration. Tilmicosin administration decreased the time to attain maximal RT (P = 0.01) by 1 h without altering the peak RT (P = 0.85), and tilmicosin interacted with energy intake to increase prechallenge PIC in 70RES vs. 70AL (P < or = 0.05). Results indicate that increased PIC response, presumably resulting from a combination of decreased energy intake and from direct effects of roughage, may be a mode of action for the slight decrease in morbidity that often occurs when newly received, stressed calves are fed roughage-based receiving diets. Tilmicosin phosphate might have immunomodulatory capacity beyond its direct effects on pathogenic bacteria, and these effects could interact with dietary energy intake in cattle.
...
PMID:Effects of dietary energy source and level and injection of tilmicosin phosphate on immune function in lipopolysaccharide-challenged beef steers. 1840 86

Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King's College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The 'low IL-6' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The 'high transcription' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the 'protective' effect of the 5-HTTLPR polymorphism was evident only in the presence of the 'low IL-6' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the 'high IL-6' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role of the inflammatory response system in the pathophysiology of IFN-alpha-induced depression; in contrast, the effect of the 5-HTT gene was small and perhaps dependent on the status of the inflammatory response.
...
PMID:Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. 1845 77

Cancer patients undergoing treatment with systemic cancer chemotherapy drugs often experience debilitating fatigue similar to sickness behavior, a normal response to infection or tissue damage caused by the production of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6. The p38 mitogen activated protein kinase (p38 MAPK) plays a central role in the production of these cytokines and consequently the development of sickness behavior. Targeted inhibitors of p38 MAPK can reduce systemic inflammatory cytokine production and the development of sickness behavior. Several systemic cancer chemotherapy drugs have been shown to stimulate inflammatory cytokine production, yet whether this response is related to a common ability to activate p38 MAPK is not known and is the focus of this study. This understanding may present the possibility of using p38 MAPK inhibitors to reduce chemotherapy-induced inflammatory cytokine production and consequently treatment-related fatigue. One caveat of this approach is a potential reduction in chemotherapeutic efficacy as some believe that p38 MAPK activity is required for chemotherapy-induced cytotoxicity of tumor cells. The purpose of this study was to demonstrate proof of principal that p38 MAPK inhibition can block chemotherapy-induced inflammatory cytokine production without inhibiting drug-induced cytotoxicity using murine peritoneal macrophages and Lewis Lung Carcinoma (LLC1) cells as model cell systems. Using these cells we assessed the requirement of etoposide, doxorubicin, 5-fluorouracil, and docetaxel for p38 MAPK in inflammatory cytokine production and cytotoxicity. Study findings demonstrate that clinically relevant doses of etoposide, doxorubicin, and 5-FU activated p38 MAPK in both macrophages and LLC1 cells. In contrast, docetaxel failed to activate p38 MAPK in either cell type. Activation of p38 MAPK mediated the drug's effects on inflammatory cytokine production in macrophages but not LLC1 cytotoxicity and this was confirmed with inhibitor studies.
...
PMID:Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-fluorouracil, and doxorubicin without affecting tumoricidal activity. 1852 41

The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint.
...
PMID:Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients. 1862 49

The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating inflammation in the periphery and brain, but whether it protects against infection- or age-related psychomotor disturbances and fatigue is unknown. Therefore, the present study evaluated motor coordination, time to fatigue, and several central and peripheral proinflammatory cytokines in male young adult (3-mo-old) and middle-aged (12-mo-old) wild-type (IL-10(+/+)) and IL-10-deficient (IL-10(-/-)) mice after intraperitoneal injection of lipopolysaccharide (LPS) or saline. No age-related differences were observed; therefore, data from the two ages were pooled and analyzed to determine effects of genotype and treatment. LPS treatment increased IL-1beta, IL-6, and TNFalpha mRNA in all brain areas examined in IL-10(+/+) and IL-10(-/-) mice, but to a greater extent and for a longer time in IL-10(-/-) mice. Plasma IL-1beta and IL-6 were increased similarly in IL-10(+/+) and IL-10(-/-) mice 4 h after LPS but remained elevated longer in IL-10(-/-) mice, whereas TNFalpha was higher in IL-10(-/-) mice throughout after LPS treatment. Motor performance and motor learning in IL-10(+/+) mice were not affected by LPS treatment; however, both were reduced in IL-10(-/-) mice treated with LPS compared with those treated with saline. Furthermore, although LPS reduced the time to fatigue in IL-10(+/+) and IL-10(-/-) mice, the effects were exacerbated in IL-10(-/-) mice. Thus the increased brain and peripheral inflammation induced by LPS in IL-10(-/-) mice was associated with increased coordination deficits and fatigue. These data suggest that IL-10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti-inflammatory effects.
...
PMID:Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation. 1865 Mar 18

We tested the hypothesis that reactive oxygen species (ROS) and inflammatory mediators affect transduction properties of muscle spindles. In rats, muscle spindles response to high-frequency vibration (HFV) was recorded before and after (1) injection of hydrogen peroxide (H2O2) in control rats and animals pre-treated with diclofenac (anti-inflammatory substance), (2) injection of bradykinin and (3) fatigue induced by muscle stimulation (MS) in control rats and rats receiving diclofenac, superoxide dismutase (SOD) or H2O2. Muscular oxidative stress and inflammation induced by H2O2 or MS were assessed by measurements of isoprostanes and IL-6 levels. In control rats, H2O2, bradykinin and MS significantly enhanced the HFV response. Pre-treatment with SOD abolished the post-MS-enhanced HFV response whereas diclofenac lowered the peak HFV response to MS and H2O2. H2O2 injection and MS elicited significant and similar increases in isoprostanes and IL-6. We report a direct modulation of muscle spindles mechanosensitivity by ROS and inflammatory mediators.
...
PMID:Reactive oxygen species and inflammatory mediators enhance muscle spindles mechanosensitivity in rats. 1884 83

Allostatic load (AL) is a theoretical framework that describes the cumulative physiologic effects of adaptation to change or stress throughout the lifespan. AL is operationalized by a composite index of multiple biomarkers. Accordingly, genes, behavior and environment contribute to AL. To determine if individual differences in AL may be influenced by inherent genetic variation, we calculated an allostatic load index (ALI) for 182 Caucasian subjects derived from a population-based study of chronic fatigue syndrome. Nearly 65% of the subjects in this study sample reported fatiguing illness. ALI was calculated based on 11 measures representing metabolic, cardiovascular, inflammatory, hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activities. Subjects were dichotomized into high (ALI > or = 3) or low (ALI < 3) AL groups, and the association between high AL and 129 polymorphisms in 32 genes related to the HPA axis, neurotransmission, inflammation, cardiovascular and metabolic functions were evaluated. Polymorphisms in angiotensin-1 converting enzyme (ACE), corticotropin-releasing hormone receptor 1 (CRHR1), and serotonin receptors (HTR3A and HTR4) were associated with AL (p=0.0007-0.0486), but only one polymorphism, rs4968591, in ACE remained significant after correction for multiple comparisons. The T allele of ACE rs4968591 was more common in subjects with high AL (67.5%) than in subjects with low AL (49.3%) (p=0.0007), and this effect appeared independent of age, sex, body mass index and fatigue status. Additionally, high interleukin-6 (IL-6; p(trend)=0.04), and C-reactive protein (CRP; p(trend)=0.01) levels, as well as low urinary cortisol levels in females (p=0.03) were associated with the T allele, which may result in allele-specific binding of the transcription factor, E2F1. Our results suggest a role for ACE in the bidirectional communication between the central nervous and immune systems in response to stress. Further studies will be needed (a) to replicate the association between AL and ACE polymorphisms in population studies designed to differentiate the effects of sex, age and racial/ethnic background, (b) to evaluate the effect of allele-specific binding of E2F1 at rs4968591, and (c) to examine the role of ACE in the co-regulation of CRP, IL-6 and cortisol.
...
PMID:An angiotensin-1 converting enzyme polymorphism is associated with allostatic load mediated by C-reactive protein, interleukin-6 and cortisol. 1908 78

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>