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      Cytokine expression in human intervertebral disc: Local distribution and comparison of cytokine levels in normal and herniated lumbar intervertebral discs

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          Abstract

          Abstract. Inflammatory mediators play an important role during the process of degeneration of the human intervertebral disc. The present study focused on a large group of cytokines and their expression in anulus fibrosus (AF) and nucleus pulposus (NP) of herniated and normal lumbar intervertebral disc. The AF and NP samples were obtained from 8 patients during surgery for herniated lumbar intervertebral disc and from 5 controls during multiorgan procurement procedure. There was no statistically significant difference in the levels of cytokines between AF and NP in the group of patients and also no statistically significant difference in the levels of cytokines between AF and NP in the group of controls. Comparison of cytokine levels in AF between patients and controls revealed significantly decreased levels of IL-6, IL-8, IL-10, MCP-1 in patients compared to controls. Comparison of cytokine levels in NP between patients and controls revealed significantly decreased levels of IL7, IL-10, GM-CSF in patients compared to controls. The results of our study support the opinion that immune reactions may play an important role in the degenerative processes in lumbar degenerative disc disease. These reactions are composed not only from a period of hyperinflammation, but also from a period of hypoinflammation. A relation between these two periods of immune system activity are still not clearly understood and require further evaluation for improving our treatment strategies.


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          Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues.

          Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. Immunoreactivity for IL-4, IL-6, IL-12, and interferon-gamma (IFNgamma) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. Greater IFNgamma positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration.
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            Copper and carcinogenesis.

            Metal ions play an important role in biological systems, and without their catalytic presence in trace or ultratrace amounts many essential co-factors for many biochemical reactions would not take place. However, they become toxic to cells when their concentrations surpass certain optimal (natural) levels. Copper is an essential metal. Catalytic copper, because of its mobilization and redox activity, is believed to play a central role in the formation of reactive oxygen species (ROS), such as O2-* and *OH radicals, that bind very fast to DNA, and produce damage by breaking the DNA strands or modifying the bases and/or deoxyribose leading to carcinogenesis. The chemistry and biochemistry of copper is briefly accounted together with its involvement in cancer and other diseases.
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              Serum ceruloplasmin and copper levels in patients with primary brain tumors.

              Serum copper and ceruloplasmin levels are known to increase in several malignancies such as osteosarcomas, some gastrointestinal tumors, and lung cancer. In this study serum copper and ceruloplasmin levels in 40 patients with primary brain tumors were studied. Both parameters were increased in sera of patients with tumors in comparison with healthy subjects or patients with non-tumorous neurological diseases. It is concluded that copper and ceruloplasmin represent a good complement to some other nonspecific parameters in evaluating the activity of malignancy and the therapeutic results.
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                Author and article information

                Journal
                Trace Elements and Electrolytes
                TE
                Dustri-Verlgag Dr. Karl Feistle
                0946-2104
                January 10 2018
                Article
                10.5414/TEX01518
                2ac05df7-b5f5-4326-9eb0-46d322d49849
                © 2018
                History

                Endocrinology & Diabetes,General medicine,Medicine,Gastroenterology & Hepatology,Nutrition & Dietetics
                lumbar intervertebral disc,cytokines level,anulus fibrosus,nucleus pulposus

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