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)

The aim of the study was to determine factors of risk and progress of aortal valvular calcinosis (AVC) and aortic ostium stenosis (AOS). The subjects were 85 patients with AVC (42--with aortic valvular stenosis (AVS), and 43--without AOS). The study, which included analysis of the lipid and mineral metabolism, and immunological tests, shows that potential factors of AVC are: age (p < 0. 001), osteoporosis (p < 0.03), mitral ring calcification (p = 0.047), dislipidemia (high serum level of total cholesterol, cholesterol of low density lipoproteins, and apoB, atherogenic shift of apoB/apoA-1 ratio, low level of cholesterol of high density lipoproteins (CHDLP)), disbalance between intecellular matrix synthesis and destruction (high concentration of alkaline phosphatase and its bone fraction, and accelerated deoxypyridinoline excretion), inflammation (high concentration of C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6)). The factors of AOS were: age (p < 0.001), smoking (p < 0.001), osteoporosis (p = 0.004), AVC (p < 0.001), mitral ring calcinosis (p = 0.033), dislipidemia (high levels of cholesterol of low density and very low density lipoproteins, low concentrations of CHDLP, and apoA-1), degradation of extracellular matrix, and inflammation (high concentrations of CRP, fibrinogen, IL-6, and IL-8). Thus, atherogenic dislipidemia and mineral dysmetabolism disorder facilitate AVC. The revealed immune status changes imply the role of inflammation in the development and progress of AVS.
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PMID:[Factors facilitating development of degenerative aortic valvular stenosis]. 1607 46

Interleukin-6 (IL-6) is a pleiomorphic cytokine whose growth factor properties play an important role in the development and progression of many types of cancer. IL-6 is produced in response to a variety of stimuli, and is required for the development of T and B lymphocytes to effector cells. In certain neoplasias, such as multiple myeloma, IL-6 is both produced and required for survival by the cancer cell itself. In other neoplasias, IL-6 may come from tissue surrounding the tumour. Thus, therapeutic strategies aimed at inhibiting the production, expression or action of IL-6 would be quite beneficial in the treatment of cancer. Moreover, IL-6 is a pathophysiological factor in several hyperproliferative diseases and the paraneoplastic syndromes that often accompany cancer, such as cachexia and osteoporosis; thus, anti-IL-6 therapy would be useful in treating these entities as well. This expert opinion acquaints the reader with IL-6, its physiological responses, the cancer types with which it is associated, and discusses the current state of therapy aimed at inhibiting it.
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PMID:Interleukin-6 and new strategies for the treatment of cancer, hyperproliferative diseases and paraneoplastic syndromes. 1608 40

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.
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PMID:Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells. 1610 54

Tumor necrosis factor (TNF) and interleukin-6 (IL-6) are pleiotropic cytokines produced by immune and nonimmune cells. Inappropriate expression and production of TNF and IL-6 is thought to be involved in the pathogenesis of numerous diseases, including atherosclerosis which leads to coronary heart disease, osteoporosis and Alzheimer's disease. Conversely, these disorders belong to the late complications of menopause and hormone replacement therapy (HRT) may successfully improve them. Several studies have shown that postmenopausal women show an enhanced expression of TNF and IL-6. On contrary, the use of hormone replacement therapy by postmenopausal women has been shown to down regulate this overexpression. Therefore, the mechanisms underlying the protective effects of HRT can also be attributed to its immunomodulating properties which seem to restore cytokine homeostasis in postmenopausal women.
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PMID:[Role of tumor necrosis factor (TNF) and interleukin-6 (IL-6) in the pathogenesis of late complications of menopause. Effects of hormone replacement therapy on TNF and IL-6 expression]. 1612 93

There may be three ways of relationship between stress and osteoporosis. The first is that stress induces some physiological changes leading to osteoporosis. The second is that stress induces behavioral distortion of eating, drinking, exercise, and sleep habits, which leads to osteoporosis. The third is that osteoporosis, on the other hand, brings about anxiety, depression, loss of social roles, and social isolation, which leads to stress. The susceptible sex and age groups are postmenopausal women and young women. The abrupt decrease of estrogen in postmenopausal women promotes reabsorption of bone, and it was also reported that the increase of interleukin-6 (IL-6) that is downstream of estrogen was related to the production of osteoclast and to the development of disability of the aged. Regarding the association with stress, while it was reported that depression or depressive states directly increased inflammation-induced cytokines including IL-6, it was also pointed out that stress-induced easy infectious may produce chronic infection, which indirectly increases inflammation-induced cytokines. Anorexia Nervosa that is assumed to be associated with adolescent developmental stress is noteworthy in young women. Amenorrhea is always present in this disease, and in addition to bone reabsorption associated with estrogen deficiency, the decrease of bone formation associated with malnutrition may be related to the development of osteoporosis.
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PMID:[Osteoporosis and stress]. 1613 56

Dietary phosphorus (P) is essential to bone growth and turnover; however, little research has focused on the genetic mechanisms controlling P utilization. Understanding the interactions between genetics and dietary P that optimize bone integrity could provide novel interventions for osteoporosis. Thirty-six pigs from two sire lines known to differ in bone structure [heavier boned (HB) and lighter boned (LB)] were assigned to one of the three diets (P adequate, P repletion or P deficient). After 14 days, bone marrow and intact radial bones were collected. Differences between these lines in growth rate, bone integrity and gene expression within bone marrow were observed. In HB, but not LB, pigs, the P-deficient diet decreased weight gain (P<.01). For both lines, P deficiency caused a reduction in radial bone strength (P<.01), but HB P-deficient animals had greater (P<.10) bone integrity than P-deficient LB pigs. In HB, but not LB, pigs, dietary treatment affected the expression of CALCR (calcitonin receptor) (P<.05), VDR (vitamin D receptor) (P<.04) and IGFBP3 (insulin-like growth factor binding protein 3) (P<.06). There was also a trend of increased IL6 (interleukin-6), TFIIB (transcription initiation factor IIB) and SOX9 (sex determining region Y-box 9) expression with P deficiency in HB, but not LB, pigs. Both genetic backgrounds responded similarly to P deficiency with an increase in the expression of OXTR (oxytocin receptor) and IGF1 (insulin-like growth factor 1). Differences in growth rate, bone integrity and gene expression within the bone marrow suggest a difference in the homeorhetic control of P utilization between these genetic lines. Understanding these differences could lead to novel treatments for osteoporosis and aid in the development of tests for identifying those at risk for this disease.
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PMID:Genetic background influences metabolic response to dietary phosphorus restriction. 1631 Oct 27

The etiology of primary osteoporosis in young and middle-aged men is unknown. We have studied osteoblast function in cells derived from men with idiopathic osteoporosis and in control cells from age-matched men with osteoarthrosis. Osteoblasts were isolated from transiliac bone biopsies. Osteoblast function was measured as vitamin D-stimulated osteocalcin production and production of cytokines and factors involved in osteoclast activation and bone formation. Cell proliferation was measured as (3)H-thymidine incorporation. Parathyroid hormone-related peptide (PTHrP) mRNA was measured using reverse-transcriptase polymerase chain reaction. In osteoporotic men, bone mineral density at the femoral neck was correlated to in vitro production of osteocalcin. Osteoblasts from osteoporotic men produced significantly less osteocalcin after vitamin D stimulation but had increased production of macrophage colony-stimulating factor (M-CSF) compared to controls. The osteocalcin response was negatively correlated to production of M-CSF, interleukin-6, and C-terminal propeptide of type I collagen. Basal (3)H-thymidine incorporation was similar in cells from osteoporotic patients and controls. PTHrP (10(-9 )M) significantly increased cell proliferation in control cells but not in osteoporotic cells. Basal PTHrP mRNA levels were significantly higher in osteoporotic cells than in cells from controls. The results are in agreement with previous histomorphologic studies indicating that men with idiopathic osteoporosis have an osteoblast dysfunction with decreased osteocalcin production and increased production of factors stimulating osteoclast activation. This indicates a catabolic cellular metabolic balance leading to negative bone turnover, resulting in osteoporosis. The cause of such cellular dysfunction needs further evaluation.
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PMID:Osteoblast dysfunction in male idiopathic osteoporosis. 1646 76

Human interleukin-6 is involved in the maintenance and progression of several diseases such as multiple myeloma (MM), rheumatoid arthritis, or osteoporosis. Our previous work demonstrated that an interleukin-6 antagonist peptide (named PT) possessed potential bioactivity to antagonize the function of hIL-6 and could efficiently induce the growth arrest and apoptosis of XG-7 and M1 cells in a dose-dependent manner. In this study, the theoretical interaction of the peptide PT with its receptor was analyzed further more with molecular docking and molecular dynamics methods. The theoretical studies showed that PT possessed very high affinity to interleukin-6R and offered a practical means of imposing long-term blockade of interleukin-6 activity in vivo. According to the theoretical results, the biological evaluation of PT was researched on two different cells models with more sensitive approaches: (1) The antagonist activity of PT was studied on the interleukin-6 dependent MM cells (XG-7) cultured with interleukin-6. In the other interleukin-6 dependent MM cells (SKO-007), they survived themselves by auto/paracrine without the exogenous interleukin-6, and also could be antagonized by PT. The therapeutic value of PT only limited on the interleukin-6 dependent category in MM. (2) Myeloid leukemia M1 cells were induced for growth arrest and apoptosis in response to interleukin-6. The results supported our previous findings and showed that PT could be evaluated by protecting the cells from interleukin-6 induced apoptosis. In conclusion, PT could induce interleukin-6-dependent XG-7 and SKO-007 cells to apoptosis while inhibit interleukin-6-stimulated apoptosis in M1 cells.
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PMID:The rational designed antagonist derived from the complex structure of interleukin-6 and its receptor affectively blocking interleukin-6 might be a promising treatment in multiple myeloma. 1662 51

The longer life expectancy of women than that of men and, therefore, the longer exposure to fracture risk has, at least partially, led to neglect of osteoporosis in men. Recently, unipolar depression, which is 2 times more frequent in women than in men, has been linked to osteoporosis. However, it is quite possible that this diagnosis may escape detection in men because of a different behavioral phenotype between the genders. A potential mechanism of bone loss in depression has been proposed, involving concurrent activation of the hypothalamo-pituitary-adrenal and sympatho-adrenal axes, suppression of the gonadal and somatotrophic axes, and high interleukin-6 and low leptin levels. We suggest that similar neurohormonal changes may cause osteoporosis in men.
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PMID:Depression and osteoporosis in men: association or casual link? 1672 81

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [OR(integral)] = 1.34, 95% confidence interval [CI] 1.10-1.63; OR(trabecular )= 1.25, 95% CI 1.02-1.53; OR(cortical )= 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.
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PMID:Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and body composition study. 1692 45


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