Juraj Sutovsky1, Martin Benco1, Martina Sutovska2, Michaela Kocmalova3, Lenka Pappova3, Juraj Miklusica4, Andrej Frano5, Egon Kurca6. 1. Neurosurgery Clinic, Jessenius Faculty of Medicine, Martin University Hospital, Comenius University, Kollarova 2, 036 01 Martin, Slovakia. 2. BioMed (Martin's Biomedical Center), Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin's Biomedical Center (BioMed), Malá Hora, 11161 4D, 036 01 Martin, Slovakia. Electronic address: sutovska@jfmed.uniba.sk. 3. BioMed (Martin's Biomedical Center), Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin's Biomedical Center (BioMed), Malá Hora, 11161 4D, 036 01 Martin, Slovakia. 4. Transplant and Vascular Surgery Clinic, Jessenius Faculty of Medicine, Martin University Hospital, Comenius University, Kollarova 2, 036 01 Martin, Slovakia. 5. The Orthopedic Clinic, 1st Medical Faculty, Charles University, Prague, the Hospital Na Bulovce, Budínova 2, 180 81 Prague 8, Czech Republic. 6. Neurological Clinic, Jessenius Faculty of Medicine, Martin University Hospital, Comenius University, Kollarova 2, 036 01 Martin, Slovakia.
Abstract
BACKGROUND: Lumbar degenerative spondylolisthesis (DS) develops as a result of inflammatory and remodeling processes in facet joints (FJs). Several inflammatory cytokines are involved in the osteoarthritic and remodeling changes that occur and in low-back and/or radicular pain, the most prevalent clinical symptom of disease. This study improves knowledge related to the roles that 27 cytokines, chemokines and growth factors play in the pathophysiology of lumbar DS. MATERIAL AND METHODS: Cytokine levels were examined using capture sandwich immunoassay using the Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) separately in intervertebral discs (IVDs) and FJ bone tissue. The samples were obtained during primary spinal surgery from 9 patients suffering from lower segment lumbar DS. The pain intensity was assessed using a visual analog scale. The controls were tissue samples collected from both lower lumbar segment levels of 6 male subjects during a multiorgan procurement procedure. RESULTS: The Bio-Plex® assay revealed significant differences between the patients and controls in cytokines, chemokines and growth factor profiles: i, The elevated interleukin-6 (IL-6), IL-7, IL-13, tumor necrosis factor α (TNF-α), interferon γ and platelet-derived growth factor levels in lumbar DS samples of subchondral FJ bone. These indicated ongoing inflammation, bone formation and increased fibroblasts activity in the FJ bone. ii, The elevated levels of IL-6, IL-8, TNF-α, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in anulus fibrosus together with increased IL-6, IL-8, TNF-α and eotaxin and decreased IL-1-receptor antagonist in nucleus pulposus confirmed advanced IVD degeneration in the patient samples. CONCLUSION: This study identified, for the first time, protective levels of cytokines, chemokines and growth factors in healthy subjects and supported their significant involvement in the pathogenesis of lumbar DS. The control samples and analytical methods used avoided any false changes in the cytokine levels due to secondary factors (e.g., death of donor and limited cytokine stability).
BACKGROUND: Lumbar degenerative spondylolisthesis (DS) develops as a result of inflammatory and remodeling processes in facet joints (FJs). Several inflammatory cytokines are involved in the osteoarthritic and remodeling changes that occur and in low-back and/or radicular pain, the most prevalent clinical symptom of disease. This study improves knowledge related to the roles that 27 cytokines, chemokines and growth factors play in the pathophysiology of lumbar DS. MATERIAL AND METHODS:Cytokine levels were examined using capture sandwich immunoassay using the Bio-Plex® 200 System and the Bio-PlexTM HumanCytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) separately in intervertebral discs (IVDs) and FJ bone tissue. The samples were obtained during primary spinal surgery from 9 patients suffering from lower segment lumbar DS. The pain intensity was assessed using a visual analog scale. The controls were tissue samples collected from both lower lumbar segment levels of 6 male subjects during a multiorgan procurement procedure. RESULTS: The Bio-Plex® assay revealed significant differences between the patients and controls in cytokines, chemokines and growth factor profiles: i, The elevated interleukin-6 (IL-6), IL-7, IL-13, tumor necrosis factor α (TNF-α), interferon γ and platelet-derived growth factor levels in lumbar DS samples of subchondral FJ bone. These indicated ongoing inflammation, bone formation and increased fibroblasts activity in the FJ bone. ii, The elevated levels of IL-6, IL-8, TNF-α, granulocyte-macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in anulus fibrosus together with increased IL-6, IL-8, TNF-α and eotaxin and decreased IL-1-receptor antagonist in nucleus pulposus confirmed advanced IVD degeneration in the patient samples. CONCLUSION: This study identified, for the first time, protective levels of cytokines, chemokines and growth factors in healthy subjects and supported their significant involvement in the pathogenesis of lumbar DS. The control samples and analytical methods used avoided any false changes in the cytokine levels due to secondary factors (e.g., death of donor and limited cytokine stability).
Authors: Aleksandra Sadowska; Ermioni Touli; Wolfgang Hitzl; Helen Greutert; Stephen J Ferguson; Karin Wuertz-Kozak; Oliver N Hausmann Journal: Eur Spine J Date: 2017-12-04 Impact factor: 3.134
Authors: Olga Krupkova; Aleksandra Sadowska; Takuya Kameda; Wolfgang Hitzl; Oliver Nic Hausmann; Juergen Klasen; Karin Wuertz-Kozak Journal: Front Immunol Date: 2018-08-17 Impact factor: 7.561