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)

The release of inflammatory cytokines caused by a disrupted disc may play a critical role in pain production at nerve endings, axons, and nerve cell bodies. Herniated disc tissue has been shown to release inflammatory cytokines such as interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor (TNF), and other algesic chemicals. This study was designed to characterize the effects of these proinflammatory cytokines on the somatosensory neural response at the dorsal root level in rats. It is hypothesized that their effects on nerve endings in disc and adjacent tissue contribute to low-back pain, and the effects on dorsal root axons and ganglia contribute to radiculopathy and sciatica. Surgically isolated sacral dorsal roots were investigated by electrophysiologic techniques. IL-1beta, IL-6, or TNF (100 ng, each) were applied onto the dorsal roots. Neural responses and mechanosensitivity of the receptive fields were evaluated over time. The results showed that 3 h after each cytokine application, the neural activity was statistically decreased. The mechanical sensitivity of the receptive fields increased at 90 min following IL-1beta or TNF application, and returned to normal more than 3 h after IL-1beta application. IL-1beta, IL-6, and TNF may be neurotoxic to dorsal root axons. Furthermore IL-1beta and TNF may sensitize the peripheral receptive fields. This study suggests that dorsal roots may be impaired by these proinflammatory cytokines.
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PMID:Dorsal root sensitivity to interleukin-1 beta, interleukin-6 and tumor necrosis factor in rats. 1238 56

There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders. This study investigated whether interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) could be detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines correlated with the severity of disease conditions. CSF samples were obtained from 21 patients with cervical myelopathy (Group M) and 19 patients with lumbar radiculopathy (Group R), and six volunteers (control). The concentration of IL-6 was significantly higher in Groups M and R than in the control, possibly demonstrating spinal cord and nerve root damage, respectively. However, TNF-alpha was lower than the detection limit. IL-1beta was detected in only five samples from three patients in Group M and two volunteers in the control. The concentrations of IL-6 did not show any correlation with symptom duration, the scoring system by the Japanese Orthopaedic Association, or the duration of nerve root block. There is a possibility that the concentration of inflammatory cytokines in CSF can indicate certain pathological aspects of cervical myelopathy or lumbar radiculopathy.
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PMID:Tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy. 1954 52

Intervertebral disc degeneration associated back pain is the most common cause of disability worldwide; however, no safe and effective treatments have been available. Here, we report a new functionalized nanofullerene conjugated with a peptide that binds specifically to a formyl peptide receptor-1 (FPR-1) expressed on activated macrophages. The new nanoparticle (aka FT-C60) was synthesized by conjugating carboxyl-C60 with the primary amine group of the peptide with a fluorescence dye for easy detection. The new nanoparticle was characterized by X-ray photoelectron spectroscopy, mass spectroscopy, and gel electrophoresis. It possessed effective radical (hydroxyl and superoxide anions) scavenging capabilities in electron paramagnetic resonance spectroscopy. In cultured cells, the nanoparticle FT-C60 demonstrated preferential binding to FPR-1 on activated macrophages and significantly attenuated mRNA expressions of proinflammatory factors including interleukin-6, interleukin-1, tumor necrosis factor-alpha, and cyclooxygenase-2. In vivo animal studies exhibited that a single intravenous injection of FT-C60 effectively alleviated pain in an established mouse model of radiculopathy for up to post-operation day (POD) 12. Ex vivo near-infrared fluorescence imaging of the mouse spine confirmed the targeting property of FT-C60 toward the injured disc on POD 14. Quantitative analysis of histological staining on spine sections showed that nanoparticle FT-C60 dramatically reduced inflammation at the local injury site compared to injury only on POD 7. In summary, we developed a novel targeted nanoparticle for treatment of lumbar radiculopathy by systemic delivery. This is a first-of-its-kind study for developing a novel class of targeted and systemic nanoparticle therapeutics to treat degenerative disc diseases.
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PMID:A New Formyl Peptide Receptor-1 Antagonist Conjugated Fullerene Nanoparticle for Targeted Treatment of Degenerative Disc Diseases. 3155 94

Up until fairly recently, it was thought that sciatic pain in the lumbar herniated disc was caused by compression on the nerve root. However, the lumbar herniated disc shows mixed pictures which are difficult to explain by simple mechanical compromise. In recent years various immunology, immunohistochemistry and molecular biology studies have shown that the herniated tissue is not an inert material, but rather it Is biologically very active with the capability of expressing a series of inflammatory mediators: cytokines such as interleukin-1, interleukin-6, interleuquin-8 and tumor necrosis factor being the ones which stand out. The inflammation is not only induced by the chemical irritation of the bioactive substances released by the nucleus pulposus but also by an autoimmune response against itself. Thus, in addition to the mechanical factor, the biomechanical mediation plays an important role in the pathophysiology of sciatic pain and of radiculopathy. Through a review of a wide range of literature, we researched the cellular molecular mediators involved in this inflammatory process around the lumbar herniated disc and its involvement in sciatic pain.
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PMID:Inflammation in the intervertebral disc herniation. 3216 19