Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium Fluoride (NaF) is the only medication so far clinically available with a bone formation stimulating property, through its peculiar mitogenic dose-dependent action on the osteoblast cell line. Bone strength is commensurate to bone mass, and in a condition with fragility fractures, like osteoporosis, it seems logical to restore bone mass without weakening bone strength. However, as with any active drug. NaF therapy requires adhesion to elementary rules if drawbacks are to be prevented. A first mandatory rule is not to prescribe NaF without calcium supplementation, if bone loss at the appendicular skeleton is to be avoided; to prevent this, the availability of monofluorophosphate (MFP), containing the fluoride and calcium salts in the same preparation has enhanced the compliance to calcium supplementation. A second rule is not to give supraphysiological doses of vitamin D, for the same reason. Third, if one wants to avoid a calcium shift from cortical to trabecular bone and osteomalacia, one should use small doses of NaF, of the order of 50 mg/day. With this in mind, the bioavailability of the drug has to be taken into account, particularly its gastrointestinal absorption which is dramatically enhanced if a plain non entericoated (EC) capsule is used, as compared to that of an EC tablet with the same face value. Too much NaF is deleterious to bone, a fact known for years. Already in 1972, it was noted that in all patients receiving 60 mg or more of NEC NaF, daily, morphologically abnormal bone developed and which appeared irregular and contained areas of incompletely mineralized bone. The bone was histologically and microradiographically normal in patients receiving 45 mg or less of NEC NaF/day. Fourth, NaF therapy is contraindicated in renal insufficiency owing to an enhanced retention in the skeleton. NaF is, however, by no means the ideal medication, because its therapeutic window is narrow. It has many bothersome drawbacks, and notably it is irritating for the gastric mucosa, a hazard which may be partly circumvented by the use of an Ec or slow release tablet. Furthermore, peripheral stress fractures may occur, and, in our experience, they were seen in 17% of patients, almost exclusively in females with a low lumbar BMD. Their occurrence should be curtailed by not allowing an increase in alkaline phosphatase activity of more than 50%. This is a relatively benign complication, because no stress fracture degenerated into a complete fracture. In all cases, the stress fractures healed after a transitory drug discontinuation. If there is some concern about cortical bone, NaF therapy may be associated with an antiresorber like estrogens which will prevent any further bone loss, and does not impair the response to NaF. NaF therapy should be reserved for patients suffering chiefly from trabecular osteoporosis and should be avoided in senile osteoporosis, because of a frequently impaired renal function. Currently, we would recommend in clinical practice a daily dose of 50 mg EC-NaF or 150 mg Ca-MFP as the therapy of involutional osteoporosis in women, reserving the dose of 75 mg EC-NAF or 200 mg MFP for males or female patients resistant to lower dose. The therapy should be maintained for 2 to 3 years, or more, according to the bone response, taking into account that patients with the vertebral crush fracture syndrome have lost on average 30%, as compard to the young adult mean.
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PMID:Fluoride therapy of type I osteoporosis. 884 58

There is little information concerning the incidence of alveolar bone loss in estrogen-deficient women. Ovariectomized sheep are valid models for study of the effects of estrogen deficiency on bone metabolism. The objective of this study was to compare alveolar bone loss in control (C) and ovariectomized sheep (OVX) at 3 and 12 months following surgery. OVX animals had decreased serum levels of 17-beta-estradiol and increased serum levels of osteocalcin, IL-6, and urinary levels of deoxypyridinoline which, taken together, suggest development of osteoporosis. The mean probing depths and percentage of sites with pocket depths 4 to 6 mm and > 6 mm were significantly greater in OVX than C at each time period and in OVX were significantly greater at 12 months that at 3 months. Gingival tissue interleukin-6 (IL-6) levels (but not the number of IL-6(+) cells) were elevated adjacent to deep periodontal pockets; however, there was no significant elevation of levels of the proinflammatory cytokines IL-1 beta and IL-8 within gingiva. Taken together, the data suggest a systemic contribution for progression of periodontal disease associated with estrogen deficiency. This may involve upregulation of systemic IL-6 synthesis and transfer to gingiva in serum, resulting in enhanced IL-6 accumulation within the gingival tissues or reduced bone density allowing for a greater amount of alveolar bone loss.
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PMID:Alveolar bone loss one year following ovariectomy in sheep. 937 31

Human osteoblasts were derived in culture from explants of bone from patients who had recently suffered osteoporotic fractures and from patients with no evidence of osteoporosis. The expression of cytokine mRNA in these osteoblasts was subsequently determined by reverse transcriptase-linked polymerase chain reaction (RT-PCR). We have detected mRNA for IL-1beta, IL-3, IL-6, IL-8, TNF-alpha and -beta, and the three TGF-beta isoforms in the cells. The profile of cytokines expressed by osteoblasts derived from patients with osteoporotic fractures was consistent with profiles observed in osteoblasts derived from patients with no evidence of reduced bone mass--the latter included children undergoing corrective surgery and adult subjects ranging from 31 to 80 years undergoing elective surgery for osteoarthritis and other bone pathologies.
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PMID:Cytokine expression by cultured osteoblasts from patients with osteoporotic fractures. 1076 43

The present study was designed to test if the serum cytokines (interleukin, or IL-1beta, -2, -2r, -6, -6r, -8, and -10, and tumor necrosis factor alpha, or TNF-alpha) and osteocalcin levels were different between 50 osteoporotic and 30 postmenopausal nonosteoporotic women and to evaluate the efficacy of calcitonin therapy during 6 months on serum cytokines and osteocalcin levels in postmenopausal osteoporotic women. In our study, serum levels of osteocalcin, TNF-alpha, IL-2, and IL-8 were significantly higher in the patient group (P < 0.05), whereas serum levels of IL-10 and IL-6r were significantly lower in the patient group (P < 0.05). When analysed separately according to bone turnover, serum levels of IL-10 and IL-6r were significantly lower in the normal-turnover group (P < 0.05), and IL-2, IL-8, and TNF-alpha were significantly higher in the high-turnover group than in the control group (P < 0.05). Statistically significant improvement seemed to happen in the patients receiving calcitonin plus calcium therapy (P < 0.05) concerning levels of serum IL-6r at the 1st month (P < 0.05), IL-10, IL-2r, IL-6r, and osteocalcin at the 3rd month, and IL-6r and osteocalcin at the end of the 6th month. Our findings demonstrate that calcitonin plus calcium therapy appears to be particularly more effective for patients with high turnover. In addition, our study suggests that IL-10 and IL-6r may have an important role in normal-turnover osteoporosis, while IL-2, IL-8, and TNF-alpha may play an important role in high-turnover postmenopausal osteoporosis.
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PMID:Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and changes during calcitonin plus calcium therapy. 1221 65

Interleukin (IL)-6 is a key mediator in the regulation and coordination of the immune response and participates in pathogenesis of cancer cachexia, autoimmune disease, and postmenopausal osteoporosis. In the course of a screening program aimed at IL-6 inhibitor from natural products, we isolated 20S,21-epoxy-resibufogenin-3-formate (ERBF) from bufadienolide and examined the effect of ERBF on activities of various cytokines. ERBF dose dependently suppressed IL-6 activity and caused a parallel rightward shift of dose-response curves to IL-6 at concentrations of 0.03 to 10 ng/ml. Analysis of data yields a pA(2) of 5.12 and a slope of 0.99. Selectivity of ERBF on activity of cytokines was examined using cytokine-dependent cell lines. ERBF did not affect IL-2-dependent growth of CTLL-2 cells, IL-3-dependent growth of Baf3 cells, or tumor necrosis factor (TNF)alpha-induced growth suppression in TNFalpha-sensitive L929 cells. ERBF also did not affect IL-4-stimulated expression of FcepsilonR II receptor (CD23) in U-937 cells, the IL-8-induced chemotaxis of human neutrophils, or nerve growth factor-stimulated neuronal differentiation in PC-12 cells. In contrast, ERBF dose dependently suppressed IL-6-induced neuronal differentiation in PC-12 cells. Furthermore, ERBF suppressed only IL-6-induced osteoclast formation without affecting osteoclast formation induced by IL-11, leukemia inhibitory factor, and 1alpha,25-dihydroxyvitamin D(3). In receptor binding assay, unbound (free) IL-6 was increased in a dose-dependent manner by pretreatment with ERBF on IL-6 receptor (IL-6R), suggesting that ERBF suppresses binding of IL-6 to IL-6R. These results clearly indicate that ERBF is a novel specific small molecule to show IL-6 receptor antagonist activity.
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PMID:Biological activity of a novel nonpeptide antagonist to the interleukin-6 receptor 20S,21-epoxy-resibufogenin-3-formate. 1223 39

The present study was designed to determine if levels of serum cytokines, such as interleukin (IL)-1beta, IL-2, IL-2r, IL-6, IL-6r, IL-8, IL-10, and TNF-alpha are different in osteoporotic and non-osteoporotic postmenopausal women, and to evaluate the effects of calcitonin and alendronate therapies over a six month period on serum cytokine levels in postmenopausal osteoporotic women. Serum levels of IL-2, TNF-alpha and IL-8 were found to be significantly higher (p < 0.05), and serum IL-10, and IL-6r significantly lower in the calcitonin (N=60) and the alendronate (N=60) treatment groups than in the control group (N=50) (p < 0.05). But, no significant difference was apparent between the calcitonin and alendronate treated groups before treatment. Statistically significant changes occurred in patients, with respect to the levels of serum IL-6r, and IL-8 after one month (p < 0.05), in IL-2r, IL-6r, IL-8, IL-10 after three months, and in IL-1beta, IL-6r, IL-8, IL-10 and TNF-alpha after six months of calcitonin therapy (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-8 and IL-10 after three months, and in TNF-alpha after six months in the calcitonin treated group and in the control group, whereas these parameters were significantly different at baseline. In the alendronate treated group, statistically significant changes occurred in the levels of serum IL-1alpha and IL-6 after three months, and in IL-1beta, IL-6, IL-6r and TNF-alpha after six months (p < 0.05). No significant difference was observed in IL-6r after one month, in IL-10 after three months or in TNF-alpha after six months between the alendronate treatment group and the control group, whereas these parameters were significantly different at baseline. In conclusion, we suggest that; 1) not only IL-1, IL-6, TNF-alpha and IL-11 but also IL-2, IL-8 and IL-10 may have roles in the etiopathogenesis of osteoporosis, 2) calcitonin therapy have a more distinct influence on serum levels of some cytokines and have an earlier effect than alendronate therapy (especially upon IL-2r, IL-8, and IL-10). Nevertheless, further longitudinal studies are needed to identify the cytokines involved in the pathogenesis of postmenopausal osteoporosis and to evaluate the influence of different treatments on these cytokines.
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PMID:The effects of alendronate and calcitonin on cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study. 1261 82

Cytokine has been postulated to play a role in the pathogenesis of post-menopausal osteoporosis. To test this hypothesis we measured circulating levels of IL-1, IL-6,IL-8 and TNF-alpha in 98 post-menopausal women (30 age matched normal and 68 osteoporotic) with no vertebral fractures. Although the cytokine levels of patients were found in normal cut off values, the difference in cytokine levels between patients and controls was statistically significant for IL-1 and IL-8 (p < 0.01). In osteoporotic patients, none of the cytokines correlated with lumbar, femoral (neck) and total hip bone mineral densities and also with body mass index (p > 0.01). In conclusion, we were unable to demonstrate abnormalities of cytokines affecting bone resorption in peripheral serum of women with post-menopausal osteoporosis. However increased production of these cytokines may occur in the local environment of bone.
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PMID:Correlation of serum cytokine levels with axial bone mineral density. 1268 May 27

This survey covered 60 post-menopausal women with osteoporosis. The patients were divided into three equal groups, and each group was treated with one of the three so-called anti-resorptive drugs, namely alendronate (10 mg/day) risedronate (5 mg/day) and raloxifene (60 mg/day) for 12 months. The Elisa technique was used to measure circulating IL-18 and MMP-9. Lumbar bone mineral density (BMD) levels were determined by using dexa mineralometry (Lunar DPX) at baseline and after 12 months of treatment. The results showed comparable responses of the patients treated with alendronate or risedronate, being a significant increase in BMD, an increase in circulating IL-18, and only slight modifications in circulating MMP-9 levels. After 12 months of treatment with raloxifene, there were minimal, non-significant increases in BMD, slight modifications in IL-18 levels, and a significant reduction in circulating MMP-9 levels. The conclusions can be drawn that all three drugs, albeit through different mechanisms, can be considered valid treatments for post-menopausal osteoporosis. Although measurements of circulating IL-8 and MMP-9 levels allowed us to differentiate the effects of the three drugs used, as of today, they have no real role in the diagnosis and/or follow-up of osteoporosis.
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PMID:Interleukin-18 (IL-18) and matrix metalloproteinase-9 (MMP-9) in post-menopausal osteoporosis. 1581 63

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

Nuclear factor-kappa B (NF-kappaB) is a transcription factor that resides in the cytoplasm of every cell and translocates to the nucleus when activated. Its activation is induced by a wide variety of agents including stress, cigarette smoke, viruses, bacteria, inflammatory stimuli, cytokines, free radicals, carcinogens, tumor promoters, and endotoxins. On activation, NF-kappaB regulates the expression of almost 400 different genes, which include enzymes (e.g., COX-2, 5-LOX, and iNOS), cytokines (such as TNF, IL-1, IL-6, IL-8, and chemokines), adhesion molecules, cell cycle regulatory molecules, viral proteins, and angiogenic factors. The constitutive activation of NF-kappaB has been linked with a wide variety of human diseases, including asthma, atherosclerosis, AIDS, rheumatoid arthritis, diabetes, osteoporosis, Alzheimer's disease, and cancer. Several agents are known to suppress NF-kappaB activation, including Th2 cytokines (IL-4, IL-13, and IL-10), interferons, endocrine hormones (LH, HCG, MSH, and GH), phytochemicals, corticosteroids, and immunosuppressive agents. Because of the strong link of NF-kappaB with different stress signals, it has been called a "smoke-sensor" of the body.
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PMID:Transcription factor NF-kappaB: a sensor for smoke and stress signals. 1638 90


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