Inflammatory biomarkers in patients with sciatica: A systematic review

Maarten J. Jungen, Bastiaan C. Ter Meulen, Tim Van Osch, Henry C. Weinstein, Raymond W.J.G. Ostelo

Research output: Contribution to JournalReview articleAcademicpeer-review

Abstract

Background: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? Methods: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. Results: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10). Conclusion: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.

Original languageEnglish
Article number156
JournalBMC Musculoskeletal Disorders
Volume20
Issue number1
DOIs
Publication statusPublished - 9 Apr 2019

Fingerprint

Sciatica
Biomarkers
Pain Measurement
C-Reactive Protein
Observational Studies
Monocyte Chemoattractant Proteins
Cohort Studies
Tumor Necrosis Factor-alpha
Cross-Sectional Studies
Chemokine CX3CL1
Outcome Assessment (Health Care)
Inflammation
Biopsy
CXC Chemokines
Interleukin-17
Phospholipases A2
Protein C
Serum
Interleukin-8
Interleukin-1

Keywords

  • Biomarkers
  • Cytokines
  • Inflammation
  • Interleukin
  • Lumbar disc herniation
  • Sciatica
  • Systematic review

Cite this

Jungen, Maarten J. ; Ter Meulen, Bastiaan C. ; Van Osch, Tim ; Weinstein, Henry C. ; Ostelo, Raymond W.J.G. / Inflammatory biomarkers in patients with sciatica : A systematic review. In: BMC Musculoskeletal Disorders. 2019 ; Vol. 20, No. 1.
@article{fde23317247845538be0ca8d8f519f55,
title = "Inflammatory biomarkers in patients with sciatica: A systematic review",
abstract = "Background: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? Methods: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. Results: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95{\%} CI, 1.1 to 10). Conclusion: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.",
keywords = "Biomarkers, Cytokines, Inflammation, Interleukin, Lumbar disc herniation, Sciatica, Systematic review",
author = "Jungen, {Maarten J.} and {Ter Meulen}, {Bastiaan C.} and {Van Osch}, Tim and Weinstein, {Henry C.} and Ostelo, {Raymond W.J.G.}",
year = "2019",
month = "4",
day = "9",
doi = "10.1186/s12891-019-2541-0",
language = "English",
volume = "20",
journal = "BMC Musculoskeletal Disorders",
issn = "1471-2474",
publisher = "BioMed Central",
number = "1",

}

Inflammatory biomarkers in patients with sciatica : A systematic review. / Jungen, Maarten J.; Ter Meulen, Bastiaan C.; Van Osch, Tim; Weinstein, Henry C.; Ostelo, Raymond W.J.G.

In: BMC Musculoskeletal Disorders, Vol. 20, No. 1, 156, 09.04.2019.

Research output: Contribution to JournalReview articleAcademicpeer-review

TY - JOUR

T1 - Inflammatory biomarkers in patients with sciatica

T2 - A systematic review

AU - Jungen, Maarten J.

AU - Ter Meulen, Bastiaan C.

AU - Van Osch, Tim

AU - Weinstein, Henry C.

AU - Ostelo, Raymond W.J.G.

PY - 2019/4/9

Y1 - 2019/4/9

N2 - Background: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? Methods: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. Results: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10). Conclusion: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.

AB - Background: This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? Methods: The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. Results: In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10). Conclusion: In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica.

KW - Biomarkers

KW - Cytokines

KW - Inflammation

KW - Interleukin

KW - Lumbar disc herniation

KW - Sciatica

KW - Systematic review

UR - http://www.scopus.com/inward/record.url?scp=85064134917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064134917&partnerID=8YFLogxK

U2 - 10.1186/s12891-019-2541-0

DO - 10.1186/s12891-019-2541-0

M3 - Review article

VL - 20

JO - BMC Musculoskeletal Disorders

JF - BMC Musculoskeletal Disorders

SN - 1471-2474

IS - 1

M1 - 156

ER -