{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:59Z","timestamp":1753891619310,"version":"3.41.2"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>An increasing number of studies have indicated the important role of cytokines in the development of depressive disturbances (DD). In medically ill patients, cytokines can provoked sickness behavior, the signs of which resemble DD. This results in alterations in behavior to limit energy expenditure and redirect it to cope with particular diseases. The aim of our study was to investigate the role of pro-inflammatory IL-6, TNF-\u03b1, and IL-1\u03b2 and anti-inflammatory IL-10 and TGF-\u03b2 in DD observed in patients suffering from pain caused by disk herniation (DH) qualified for surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>The intensity of DD assessed by using Beck Depression Inventory, pain intensity, and functional impairment were evaluated in 70 patients with DH who were qualified for surgery. Pro-inflammatory serum levels of TNF-\u03b1, IL-1, IL-6, anti-inflammatory TGF-\u03b2, and IL-10 were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elevated serum levels of TGF-\u03b2, IL-10, and IL-6 were found in the group with moderate and severe depressive symptoms (SD) compared with the groups with mild (MD) or no depressive symptoms (ND). TGF-\u03b2 levels were negatively correlated with pain intensity, as assessed using the Present Pain Intensity scale in SD. Functional impairment measured using the Oswestry Disability Index was the most advanced in SD group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Results of our study can suggest association between depressive disturbances and anti-inflammatory cytokines TGF-\u03b2 and IL-10. Functional impairment of SD group is more severe but serum levels of TGF-\u03b2 and IL-10, which are involved in the healing processes, are increased.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2024.1366559","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T04:30:56Z","timestamp":1712291456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered serum cytokines in patients with symptomatic disk herniation and depressive symptoms"],"prefix":"10.3389","volume":"18","author":[{"given":"Joanna","family":"Bielewicz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Daniluk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Kamieniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ydbio.2004.08.027","article-title":"Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones","volume":"276","author":"Baffi","year":"2004","journal-title":"Dev. Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e270421185135","DOI":"10.2174\/1871526520666200820093924","article-title":"Determining serum levels of IL-10 and IL-17 in patients with low Back pain caused by lumbar disc degeneration","volume":"21","author":"Banimostafavi","year":"2021","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/hup.717","article-title":"IL-6 levels decrease with SSRI treatment in patients with major depression","volume":"20","author":"Basterzi","year":"2005","journal-title":"Hum. Psychopharmacol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"An inventory for measuring depression","volume":"4","author":"Beck","year":"1961","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5337483","DOI":"10.1155\/2022\/5337483","article-title":"VAS and NRS, same or different? Are visual analog scale values and numerical rating scale equally viable tools for assessing patients after microdiscectomy?","volume":"2022","author":"Bielewicz","year":"2022","journal-title":"Pain Res. Manag."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1097\/00000658-199611000-00009","article-title":"Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?","volume":"224","author":"Biffl","year":"1996","journal-title":"Ann. Surg."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.joca.2007.02.005","article-title":"TGF-beta and osteoarthritis","volume":"15","author":"Blaney Davidson","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.jad.2021.06.037","article-title":"Interleukin-10 level is associated with post-stroke depression in acute ischaemic stroke patients","volume":"293","author":"Chi","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1590\/S1413-78522013000300003","article-title":"Extracellular matrix remodeling in experimental intervertebral disc degeneration","volume":"21","author":"de Oliveira","year":"2013","journal-title":"Acta Ortop. Bras."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.jpsychires.2009.05.010","article-title":"Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression","volume":"43","author":"Dhabhar","year":"2009","journal-title":"J Psych Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S34","DOI":"10.1002\/eji.200737772","article-title":"Historical insights into cytokines","volume":"37","author":"Dinarello","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.neubiorev.2005.03.023","article-title":"Cytokines as mediators of depression: what can we learn from animal studies?","volume":"29","author":"Dunn","year":"2005","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1744-8069-5-16","article-title":"Transforming growth factor-beta 1 impairs neuropathic pain through pleiotropic effects","volume":"5","author":"Echeverry","year":"2009","journal-title":"J. Mol. Pain"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1097\/00007632-200011150-00017","article-title":"The Oswestry disability index","volume":"25","author":"Fairbank","year":"2000","journal-title":"Spine"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroscience.2013.04.060","article-title":"Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications","volume":"246","author":"Felger","year":"2013","journal-title":"Neuroscience"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"a022210","DOI":"10.1101\/cshperspect.a022210","article-title":"TGF-\u03b2 signaling in control of cardiovascular function","volume":"10","author":"Goumans","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"114125","DOI":"10.1016\/j.expneurol.2022.114125","article-title":"Interleukin-10 deficiency aggravates traumatic brain injury in male but not female mice","volume":"355","author":"Gu","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.bbi.2015.06.001","article-title":"Cumulative meta-analysis of interleukins 6 and 1\u03b2, tumour necrosis factor \u03b1 and C-reactive protein in patients with major depressive disorder","volume":"49","author":"Haapakoski","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/s0149-7634(88)80004-6","article-title":"Biological basis of the behavior of sick animals","volume":"12","author":"Hart","year":"1988","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.3390\/cells10061382","article-title":"TGF-\u03b2\/Smad Signalling in neurogenesis: implications for neuropsychiatric diseases","volume":"10","author":"Hiew","year":"2021","journal-title":"Cells"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2724","DOI":"10.1016\/j.spinee.2014.04.017","article-title":"Detrimental effects of discectomy on intervertebral disc biology can be decelerated by growth factor treatment during surgery: a large animal organ culture model","volume":"14","author":"Illien-J\u00fcnger","year":"2014","journal-title":"Spine J."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12891-019-2541-0","article-title":"Inflammatory biomarkers in patients with sciatica: a systematic review","volume":"20","author":"Jungen","year":"2019","journal-title":"BMC Musculoskelet. Disord."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neulet.2015.03.001","article-title":"Interleukin-10 levels in rat models of nerve damage and neuropathic pain","volume":"592","author":"Khan","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.pnpbp.2015.06.008","article-title":"The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression","volume":"64","author":"Kim","year":"2016","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychatry"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.pnpbp.2007.03.004","article-title":"Cytokine imbalance in the pathophysiology of major depressive disorder","volume":"31","author":"Kim","year":"2007","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"5385","DOI":"10.1523\/JNEUROSCI.4405-13.2014","article-title":"TGF-\u03b2 and opioid receptor signaling crosstalk results in improvement of endogenous and exogenous opioid analgesia under pathological pain conditions","volume":"34","author":"Lantero","year":"2014","journal-title":"J. Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1038\/s41386-018-0154-1","article-title":"Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signalling","volume":"43","author":"Laumet","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e00361","DOI":"10.1042\/BSR20160187","article-title":"Inflammation in low back pain may be detected from the peripheral blood: suggestions for biomarkers","volume":"36","author":"Li","year":"2016","journal-title":"Biosci. Rep."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.jad.2011.08.003","article-title":"Interleukin (IL)-6, tumour necrosis factor alpha (TNF-\u03b1) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression","volume":"139","author":"Liu","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.3390\/jcm10184142","article-title":"Biomarkers of post-COVID depression","volume":"10","author":"Lorkiewicz","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/0304-3959(87)91074-8","article-title":"The short-form McGill pain questionnaire","volume":"30","author":"Melzack","year":"1987","journal-title":"Pain"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1080\/08964289.2011.609192","article-title":"Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors","volume":"37","author":"Meyer","year":"2011","journal-title":"Behav. Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","article-title":"Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression","volume":"65","author":"Miller","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.pain.2006.07.009","article-title":"Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain","volume":"126","author":"Milligan","year":"2006","journal-title":"Pain"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"a021873","DOI":"10.1101\/cshperspect.a021873","article-title":"TGF-beta and the TGF-beta family: context-dependent roles in cell and tissue physiology","volume":"8","author":"Morikawa","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and functions of the IL-10 family of cytokines in inflammation and disease","volume":"29","author":"Ouyang","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref1001","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.bbi.2018.09.010","article-title":"Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease","volume":"75","author":"Palada","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref38","first-page":"417","article-title":"Inwentarz Depresji Becka w ocenie nastroju os\u00f3b zdrowych i chorych na choroby afektywne (ocena pilota\u017cowa)","volume":"11","author":"Parnowski","year":"1977","journal-title":"Psychiatr. Pol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1097\/01.brs.0000201324.45537.46","article-title":"Possible pathogenesis of painful intervertebral disc degeneration","volume":"31","author":"Peng","year":"2006","journal-title":"Spine"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"110289","DOI":"10.1016\/j.cbi.2022.110289","article-title":"Transforming growth factor-\u03b2 signaling: from tissue fibrosis to therapeutic opportunities","volume":"369","author":"Ren","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"187894","DOI":"10.1155\/2009\/187894","article-title":"Interleukin-10: a key cytokine in depression?","volume":"2009","author":"Roque","year":"2009","journal-title":"Cardiovasc. Psychiatry Neurol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.cytogfr.2010.09.002","article-title":"Biology of Interleukin-10","volume":"21","author":"Sabat","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1002\/ejp.1947","article-title":"Mechanism underlying painful radiculopathy in patients with lumbar disc herniation","volume":"26","author":"Samuelly-Leichtag","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e20190418","DOI":"10.1084\/jem.20190418","article-title":"Biology and therapeutic potential of interleukin-10","volume":"217","author":"Saraiva","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41573-022-00557-6","article-title":"Emerging principles of cytokine pharmacology and therapeutics","volume":"22","author":"Saxton","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3171\/2013.1.SPINE12483","article-title":"Chemokine profile of disk degeneration with acute or chronic pain","volume":"18","author":"Schroeder","year":"2013","journal-title":"J. Neurosurg. Spine"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/0306-9877(91)90272-z","article-title":"He macrophage theory of depression","volume":"35","author":"Smith","year":"1991","journal-title":"Med. Hypotheses"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1007\/s00586-015-4349-4","article-title":"A cohort study comparing the serum levels of pro-or anti-inflammatory cytokines in patients with lumbar radicular pain and healthy subjects","volume":"25","author":"Wang","year":"2016","journal-title":"Eur. Spine J."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.psychres.2019.01.100","article-title":"Interleukin-6 and Interleukin-10 in mood disorders: a population-based study","volume":"273","author":"Wiener","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/s12974-020-01922-1","article-title":"Anti-inflammatory IL-10 administration rescues depression-associated learning and memory deficits in mice","volume":"17","author":"Worthen","year":"2020","journal-title":"Neuroinflammation"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.bbi.2018.06.015","article-title":"Spinal interleukin-10 produces antinociception in neuropathy through microglial \u03b2-endorphin expression, separated from antineuroinflammation","volume":"73","author":"Wu","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bbi.2021.06.015","article-title":"Depression-like behavior associated with E\/I imbalance of mPFC and amygdala without TRPC channels in mice of knockout IL-10 from microglia","volume":"97","author":"Yang","year":"2021","journal-title":"Brain Behav. Immun."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1366559\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T04:30:59Z","timestamp":1712291459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1366559\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,5]]},"references-count":54,"alternative-id":["10.3389\/fnins.2024.1366559"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2024.1366559","relation":{},"ISSN":["1662-453X"],"issn-type":[{"type":"electronic","value":"1662-453X"}],"subject":[],"published":{"date-parts":[[2024,4,5]]},"article-number":"1366559"}}