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

In the reconstruction of a segmental defect in injured peripheral nerves, gradual nerve elongation has become an important alternative to nerve grafting. To clarify biochemical responses in peripheral sensory neurons after nerve elongation, we examined the expression of cytokines and neurotrophins related to nerve regeneration. We first established rat elongation models by lengthening left femurs up to 20.0 mm at the rate of 1.0, 2.0, or 20.0 mm/day. In toluidine blue staining, the acutely elongated, 20-mm/day group showed nuclear eccentricity in the nerve cell body in L5 dorsal root ganglion (DRG) and axonal degeneration in the sciatic nerves; in contrast, the gradually elongated, 1- and 2-mm/day groups remained intact, indicating adaptation. Reverse transcription-polymerase chain reaction analysis revealed that interleukin-6 (IL-6) mRNA was induced in ipsilateral L4-6 DRG in an elongation rate-dependent manner. In contrast, none of the elongated groups exhibited a significant change in mRNA levels for interleukin-1beta, tumor necrosis factor-alpha, nerve growth factor, brain-derived neurotrophic factor, neurotropnin-3, and neurotrophin-4/5. Levels of IL-6 mRNA in all the elongated groups reached the maximum level at day 4 after 20-mm lengthening, while the axotomized group showed a decrease from the maximum level at day 1. Induction of IL-6 mRNA was also detected in the contralateral L4-6 DRG of all the elongated groups, but not detected in the axotomized group. In histochemical analysis, IL-6-immunoreactivity was predominant in neurofilament-positive, medium to large DRG neurons. Application of IL-6 to cultured Schwann cells increased mRNA for peripheral myelin protein 22 (PMP22), a major myelin component. These results suggest that IL-6 plays a key role in biochemical responses in peripheral sensory neurons after gradual nerve elongation.
 ...
PMID:Induction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve. 1591 8

Twenty consecutive rheumatoid arthritis (RA) patients (mean age 50.4 +/- 10.5 years; 17 females; mean disease duration 5.78 +/- 3.75 years) enrolled for tumor necrosis factor-alpha (TNF-alpha) blockers therapy (10 infliximab and 10 etanercept) were selected. Before starting therapy, 3 and 6 months thereafter all patients were evaluated for disease activity score (DAS), erythrocyte sedimentation rate (ESR), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). After 3 and 6 months a significant reduction in DAS, ESR, CRP, and IL-6 was observed, whereas no significant differences of NGF and BDNF serum levels were found. These preliminary results confirm that TNF-alpha blockers significantly improve disease activity and inflammation in RA; nevertheless further studies are needed to explain the mechanisms regulating NGF and BDNF release in RA patients treated with TNF-alpha blockers.
 ...
PMID:Nerve growth factor and brain-derived neurotrophic factor levels in patients with rheumatoid arthritis treated with TNF-alpha blockers. 1685 71

Brain cytokine mRNA levels are impacted by systemic cytokines. For example, systemic interleukin-1beta (IL1beta) increases brain IL1beta mRNA; subdiaphragmatic vagotomy blocks this effect. To localize which brain regions respond to intraperitoneal cytokines, we measured mRNA levels in selected brain regions for a variety of cytokines and growth factors, IL1beta, TNFalpha, interleukin-6 (IL-6), interleukin-10 (IL10), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Relative to saline administration, IL1beta increased IL1beta, TNFalpha and IL6 mRNAs in the nucleus tractus solitarius (NTS), hypothalamus, hippocampus and somatosensory cortex (SSctx), but did not induce any changes in IL10. TNFalpha also increased TNFalpha and IL1beta mRNAs in the hypothalamus, hippocampus and SSctx. TNFalpha increased TNFalpha, IL1beta and IL10 mRNAs in the NTS, but did not induce any changes in IL-6 mRNA. In the amygdala, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNAs. In the insular cortex, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNA. TNFalpha administration increased NGF mRNA in the SSctx but decreased NGF and BDNF mRNA levels in the insular cortex. Both IL1beta and TNFalpha decreased BDNF mRNA in the amygdala. We also verified the IL1beta-induced increases in TNFalpha mRNA within the NTS using in situ hybridization. These results support the hypothesis that somnogenic doses of IL1beta and TNFalpha enhance their own mRNA levels as well as affect mRNA levels for other sleep-promoting substances.
 ...
PMID:Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1beta or tumor necrosis factor alpha. 1702 49

In the present study, we examined the effects of olanzapine on plasma levels of catecholamine metabolites, brain-derived neurotrophic factor, and cytokines (interleukin-2, interleukin-6 and tumor necrosis factor-alpha) using 32 olanzapine-treated schizophrenic patients and age and sex-matched 55 healthy individuals. Treatment with olanzapine for 8 weeks improved both positive and negative symptoms of schizophrenia. It also increased the plasma 3-methoxy-4-hydroxyphenylglycol levels, which were associated with the changes in the total scores of negative symptoms measured on the Positive and Negative Symptom Scale, and decreased the plasma homovanillic acid levels. In addition, treatment with olanzapine for 8 weeks reduced the plasma interleukin-2 levels. In contrast, olanzapine did not alter the plasma levels of brain-derived neurotrophic factor, interleukin-6, or tumor necrosis factor-alpha. These results suggest that olanzapine influences the dynamics of catecholamine and interleukin-2, which might be associated with its clinical efficacy.
 ...
PMID:Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. 1715 56

Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.
 ...
PMID:Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice. 1716 28

Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.
 ...
PMID:Consensus paper of the WFSBP Task Force on Biological Markers: biological markers in depression. 1962 59

This study investigates the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), on neurodegeneration, gliosis and changes in the neurotrophic protein brain-derived neurotrophic factor (BDNF) and in pro-inflammatory cytokines, following kainic acid (KA)-induced excitotoxic damage in the rat. Male Sprague-Dawley rats were treated with alpha-MSH (intraperitoneally, i.p.) at 20 min, and 24 and 48 h following administration of 10 mg/kg KA (i.p.). The animals were sacrificed at 30 min, 4 h, 24 h and 72 h after KA-administration and the levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were analysed in samples of hippocampus and hypothalamus. Levels of BDNF were analysed in the hippocampus. Stereological quantification showed a markedly reduced number of viable neurons in the CA1 pyramidal cell layer upon KA-administration as compared to animals injected with vehicle (p < 0.05, 79,587 +/- 25,554 vs. 145,254 +/- 27,871). The number of viable neurons upon administration of alpha-MSH was significantly higher than upon KA alone (p < 0.05, 119,776 +/- 33,158, KA+alpha-MSH vs. 79,587 +/- 27,554, KA + Saline). Astrocyte activation due to the KA-induced excitotoxicity was reduced, and the KA-induced increase in IL-1beta levels was delayed by the treatment with alpha-MSH. In conclusion, the degree of reduction in cell viability in the hippocampus CA1 pyramidal cell layer upon KA-induced excitotoxicity was similar to that seen previously upon global cerebral ischaemia. Furthermore, the administration of alpha-MSH resulted in a similar increase in cell viability, supporting the hypothesis that administration of alpha-MSH has rescuing effects on neurons subjected to excitotoxic insults.
 ...
PMID:Alpha-MSH rescues neurons from excitotoxic cell death. 1795 33

Impaired fine motor functions after traumatic brain injury (TBI) in humans and non-human primates often continue to improve months after injury. To initiate a series of studies in the primate model designed to investigate possible involvement of microglia/macrophage in the long-term recovery processes, changes in these cells were studied in the rhesus monkey central nervous system at 1, 6, and 12 months after a combined unilateral lesion of the arm area of the primary motor cortex and arm area of the lateral premotor cortex. Immunohistological studies showed profound CD68 immunoreactivity in the lesion area and the contralateral lateral corticospinal tract in the spinal cord at all time points, demonstrating that microglia/macrophage remain reactive at the sites of injury and axonal degeneration/survival for at least 12 months. We also observed marked increases in brain-derived neurotrophic factor (BDNF) and its receptor subtypes, TrkB[gp145] and TrkB[TK-], around the cortical lesion site after 6-month survival. Similar increases were also observed in the spinal cord, although it was less apparent for TrkB[gp145]. Double-labeling revealed that a subpopulation of CD68-immunoreacitve microglia/macrophage co-expressed BDNF in the cortex and spinal cord, and also TrkB[gp145] or TrkB[TK-] in the spinal cord. In contrast, cytokine expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) at these time intervals was less prominent, suggesting that immediate inflammatory responses had subsided. These results demonstrate that microglia/macrophage undergo prolonged activation after TBI in the non-human primate brain and express BDNF and its receptors, suggesting their tropic/trophic roles in the long-term recovery processes.
 ...
PMID:Prolonged microgliosis in the rhesus monkey central nervous system after traumatic brain injury. 1800 Dec 2

There is growing evidence that blood levels of brain-derived neurotrophic factor (BDNF) and catecholamine, and cytokines are related to not only to depressive, suicidal, and anxious states but also to depression-associated personality traits. Psychological job stress is well known to lead to symptoms of depression and anxiety. In the present study, we examined effects of psychological job stress on serum levels of BDNF and plasma levels of catecholamine metabolites, and cytokines in healthy volunteers (n=106, male/female=42/64, age=36+/-12 yr) working in a hospital setting. The values (mean+/-SD) of scores for stress items in the Stress and Arousal Check List (s-SACL), plasma MHPG levels, and, serum BDNF levels in all participants were 7.2+/-3.3, 5.2+/-3.4 ng/mL, and 23.3+/-14.7 ng/mL, respectively. A negative correlation was found between scores for s-SACL and serum BDNF levels (rho=-0.211, p=0.022). A positive correlation was also found between scores on the s-SACL and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) (rho=0.416, p=0.01), but not homovanillic acid (HVA). No relationship was found between s-SACL scores and plasma levels of interleukin-6 (IL-6) or tumor necrosis factor alpha (TNFalpha). These results suggest that serum BDNF levels and plasma MHPG levels might be biological markers reflective of psychological job stress in hospital employees.
 ...
PMID:Stress at work alters serum brain-derived neurotrophic factor (BDNF) levels and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in healthy volunteers: BDNF and MHPG as possible biological markers of mental stress? 1816 Jan 97

Amphotericin B (AmB) is a polyene antibiotic and reported to have therapeutic effects on prion diseases, in which the microglial activation has been suggested to play important roles by proliferating and producing various factors such as nitric oxide, proinflammatory cytokines, and so on. However, the therapeutic mechanism of AmB on prion diseases remains elusive. In the present study, we investigated the effects of AmB on cellular functions of rat primary cultured microglia. We found that AmB, similarly as lipopolysaccharide (LPS), could activate microglia to produce nitric oxide via inducible nitric oxide synthase. Both AmB and LPS also induced mRNA expressions of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in microglia. AmB also changed the expression levels of neurotrophic factors mRNAs. AmB and LPS significantly down-regulated the level of ciliary neurotrophic factor mRNA. However, AmB, but not LPS, significantly up-regulated the level of glial cell-line derived neurotrophic factor mRNA in microglia. In addition, brain-derived neurotrophic factor mRNA expression level was tending upward by treatment with AmB, but not with LPS. Taken together, these results suggest that AmB regulates the microglial activation in different manner from LPS and that microglia may participate in the therapeutic effects of AmB on prion diseases by controlling the expression and production of such mediators.
 ...
PMID:Effects of Amphotericin B on the expression of neurotoxic and neurotrophic factors in cultured microglia. 1832 1


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