Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 13-year-old girl presented with general fatigue, back pain, anemia, hyperimmunoglobulinemia, and a mediastinal mass on chest radiograph. A mass was surgically removed, and its histologic examination determined the diagnosis of giant lymph node hyperplasia (Castleman's disease). With removal of the hyperplastic lymph node, the clinical symptoms soon disappeared and the abnormal laboratory findings were markedly improved within 1 month: serum IgG levels decreased from 4350 mg/dl to 1829 mg/dl. Immunostaining on the lymph node sections revealed polyclonal B-lymphocyte and T-lymphocyte populations. The patient's lymph node cells were cultured without any mitogenic stimulation, and the culture supernatants were assayed for their B-cell differentiation factor (BCDF) activity to induce IgG production by our Epstein-Barr virus-transformed cell line. The patient's lymph node cells produced high levels of BCDF activity: the supernatants could increase the IgG production from 140 ng/ml to 410 ng/ml when the values became from 140 ng/ml to 142 ng/ml or 148 ng/ml with those of the control lymph node cells. These results suggest that the hyperimmunoglobulinemia and its prompt improvement with removal of the hyperplastic lymph node may have been related to the spontaneous production of high levels of BCDF activity by the lymph node cells in the patient.
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PMID:Giant lymph node hyperplasia (Castleman's disease) with spontaneous production of high levels of B-cell differentiation factor activity. 264 33

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS. Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group. Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.
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PMID:Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. 749 49

To evaluate the hematologic effects of recombinant human interleukin-6 (rhIL-6, Escherichia coli, SDZ ILS 969, IL-6), and determine its toxicity profile, we performed a phase I trial of IL-6 in 22 patients with various myelodysplastic syndromes (MDS), platelet counts < 100,000/microL, and < 5% bone marrow (BM) blasts. Patients received one of four doses of IL-6 (1.0, 2.5, 3.75, and 5.0 micrograms/kg/d) as a subcutaneous injection on day 1, followed by a 7-day wash-out period, and then 28 days of IL-6 therapy. Dose-limiting toxicities of fatigue, fever, and elevated alkaline phosphatase were seen at 5.0 micrograms/kg/d; the maximum tolerated dose was 3.75 micrograms/kg/d. All patients experienced at least grade II fever and all had an increase in acute phase proteins. Eight patients (36%) experienced at least a transient improvement in platelet counts; three fulfilled the criteria for response, whereas five others had clinically significant increases that failed to meet response criteria. Various IL-6-related toxicities prevented more than three patients from receiving maintenance therapy. Two of the three patients who received maintenance IL-6 therapy had a persistent increase in platelet counts, during 3 and 12 months of IL-6 therapy, respectively. Laboratory studies indicated that IL-6 increased the frequency of higher ploidy megakaryocytes but did not significantly increase the number of assayable megakaryocytic progenitor cells, suggesting that IL-6 acts as a maturational agent rather than a megakaryocyte colony-stimulating factor. Although IL-6 therapy can promote thrombopoiesis in some MDS patients, its limited activity and significant therapy-related toxicity preclude its use as a single agent in this patient population. Further studies, combining low doses of IL-6 with other hematopoietic growth factors, are underway.
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PMID:A phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocytopenia. 753 15

Administration of endotoxin in the evening has been shown to transiently suppress rapid eye movement (REM) and to promote non-REM sleep in humans. In a single-blind placebo-controlled crossover design, we assessed the effects of Salmonella abortus equi endotoxin administered intravenously in the morning on the primary host response and on daytime sleep by use of a multiple napping protocol in healthy volunteers. The extent of the host response achieved by 0.8 ng of endotoxin per kg of body weight given at 0900 h was comparable to that previously reported to result from the administration of 0.4 ng/kg at 1900 h. However, sleep was only slightly influenced. Endotoxin reduced the amount of REM sleep and increased REM latency. Non-REM sleep amount in the first nap, although not significantly changed, correlated negatively with the individual peak levels of interleukin-6 (r = -0.73, P < 0.05). Subjective tiredness, sleep onset latency, total sleep time, and the amounts of slow-wave and non-REM sleep were not affected by endotoxin throughout the entire experiment. Spectral analysis of the electroencephalogram obtained during non-REM sleep yielded no condition differences. We conclude that endotoxin administration in the morning to healthy volunteers, while activating the host defense to the same extent as a lower dose that has been reported to promote non-REM sleep when given in the evening, does not affect non-REM sleep. REM sleep suppression is, to date, the most consistently reported effect of endotoxin on human sleep.
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PMID:Influence of endotoxin on daytime sleep in humans. 860 66

Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive 0.5, 1, 3, 7, 10, or 30 micrograms/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo subcutaneously 3 times a week for 2 weeks. Dose-limiting toxicity, consisting of febrile reactions in some patients, fatigue, and nonproductive cough, was observed at a dose level of 30 micrograms/kg. Dose-related changes in parameters of the acute-phase response were noted, consistent with the relationship of CNTF and its receptor system to the cytokine interleukin-6 (IL-6) and its receptor. No adverse neurologic consequences of rHCNTF administration were observed. Antibodies to rHCNTF were observed in sera of most patients tested after 2 weeks of continuous treatment and 4 weeks' withdrawal period. rHCNTF was safe and tolerated within acceptable limits when administered to patients with ALS in this study at doses of up to 30 micrograms/kg 3 times a week for 2 weeks. Further studies to explore the efficacy of rHCNTF in the treatment of human motor neuron diseases are justified.
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PMID:A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group. 868 12

In patients with Lyme neuroborreliosis, inflammation and symptoms of fatigue and malaise occur out of proportion to the relatively low number of spirochetes present. Previous studies have identified interleukin-6 (IL-6) as a candidate molecule for amplification of CNS inflammation in this disease. We pursued this possibility by measuring cytokine gene expression by reverse-transcriptase polymerase chain reaction (RT-PCR) in the brain of rhesus macaques actively infected with Borrelia burgdorferi. Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product. The number of copies in positive samples was then quantitated using qRT-PCR-ELISA, in which wild-type cytokine cDNA competes with recombinant competitor DNA in the PCR. Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines. These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis.
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PMID:Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis. 922 83

A new xenograft model of multiple myeloma (MM), where growth is strongly regulated by interleukin-6 (IL-6), was established in severe combined immunodeficiency (SCID) mice. In this model, endogenous IL-6 from SCID mice was ineffective at eliciting growth of the established human MM cell line KPMM2; these cells achieved autonomous growth through their autocrine secretion of IL-6. The etiopathology in this disease model is consistent with that of human MM. When greater than 3 x 10(6) KPMM2 cells were injected intravenously (IV), tumors developed in all mice and were predominantly localized in their bone marrow. Tumors were also apparent in the lymph nodes, but absent from other organs. Immunostaining of cell surface antigen (CD38) showed that more than 40% of bone marrow cells in femur were of myeloma origin in the advanced stage of tumor progression (day 37). Histologic analysis of these mice show that bone marrow was largely occupied by plasmablastic cells and bones had developed osteolytic lesions at multiple sites. Concurrently, there was a decrease in bone density throughout the body and a significant increase in ionized plasma calcium. M-protein was detected in the serum within 10 days after transplantation, which correlated with the tumor progression. Between 30 and 40 days after the transplantation, mice presented with a rapid and severe loss of body weight, hind leg paralysis, and fatigue. Subsequently, the mice died within a week. A single IV injection of 0.2 mg humanized anti-IL-6 receptor antibody (hPM1) into mice on the day after tumor transplantation substantially suppressed the elevation of serum M-protein and development of the tumor-associated abnormalities and significantly increased in the life span of tumor-bearing mice. Our data show the usefulness of this model to analyze the pathologic role of IL-6 in MM and the efficacy of targeting the IL-6 receptor in IL-6-dependent KPMM2 cells.
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PMID:New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor. 931 Apr 95

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.
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PMID:Phase I study of interleukin-6 in children with solid tumours in relapse. 938 24

Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
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PMID:The pathophysiologic roles of interleukin-6 in human disease. 944 73

Fatigue occurs in more than 70% of patients treated with interferon-alpha (IFN-alpha) and is the most problematic toxicity associated with IFN-based immunotherapy. Abundant evidence suggests that immune-mediated endocrine disease occurs during IFN-alpha therapy, which may contribute to the etiology of fatigue. Autoimmune thyroid disease is a well-recognized consequence of IFN-alpha therapy and may be mediated by the induction of IFN-gamma production by lymphocytes. Administration of exogenous IFN-gamma has been associated with upregulation of class II major histocompatibility antigens in the thyroid and the development of thyroiditis. Interferon-alpha also stimulates the production of interleukin-6; both interleukin-6 and IFN-gamma have specific effects on thyrocyte function. There also is evidence suggesting that IFN-alpha initiates a cytokine cascade that effects the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, thus affecting regulation of glucocorticoid and sex steroid hormone secretion, but the clinical significance of these observations has not been established. Although endocrine disease will not explain the occurrence of fatigue symptoms in all patients, there is clear evidence that hormonal deficiency syndromes occur in a relatively large portion of patients receiving systemic IFN-alpha therapy. Most importantly, the possibility of hypothyroidism must be considered; however, diagnosis of hypothyroidism in cancer patients is complicated by the occurrence of the "sick euthyroid syndrome." Clinical recommendations for assessment and treatment of IFN-alpha-induced fatigue are offered. Most importantly, measurements of thyroid-stimulating hormone and antithyroid autoantibodies should be used to evaluate thyroid status. Acknowledging the limitations of current clinical data, adrenal- and gonadal-axis dysfunction also must be considered in patients with IFN-alpha-induced fatigue.
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PMID:Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha. 948 41


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