Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes

E Gjefsen; K Gervin; L C H Bråten; G L Goll; H C D Aass; E I Schistad; M Wigemyr; L M Pedersen; J S Skouen; M D Vigeland; K K Selmer; K Storheim; J A Zwart

doi:10.1016/j.joca.2023.01.001

Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes

Osteoarthritis Cartilage. 2023 Apr;31(4):543-547. doi: 10.1016/j.joca.2023.01.001. Epub 2023 Jan 12.

Authors

E Gjefsen¹, K Gervin², L C H Bråten³, G L Goll⁴, H C D Aass⁵, E I Schistad⁶, M Wigemyr⁷, L M Pedersen⁸, J S Skouen⁹, M D Vigeland¹⁰, K K Selmer¹¹, K Storheim¹², J A Zwart¹³

Affiliations

¹ Research and Communication Unit for Musculoskeletal Health (FORMI), Oslo University Hospital HF, Ulleval, Bygg 37b, P.O. Box 4956 Nydalen, 0424 Oslo, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: e.gjefsen@gmail.com.
² Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway. Electronic address: kristina.gervin@farmasi.uio.no.
³ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway. Electronic address: l.c.h.braten@ous-research.no.
⁴ Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway. Electronic address: GuroLovik.Goll@diakonsyk.no.
⁵ Department of Medical Biochemistry, Oslo University Hospital, Norway. Electronic address: h.c.aass@medisin.uio.no.
⁶ Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Norway. Electronic address: UXIOEL@ous-hf.no.
⁷ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway. Electronic address: UXWMON@ous-hf.no.
⁸ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway; Department of Physiotherapy, Oslo Metropolitan University, Norway. Electronic address: limped@ous-hf.no.
⁹ The Outpatient Spine Clinic, Department of Physical Medicine and Rehabilitation, Haukeland University Hospital, Bergen, Norway. Electronic address: jan.sture.skouen@helse-bergen.no.
¹⁰ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: mariadvi@studmed.uio.no.
¹¹ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway. Electronic address: k.k.selmer@medisin.uio.no.
¹² Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway; Department of Physiotherapy, Oslo Metropolitan University, Norway. Electronic address: kjersti.storheim@ous-research.no.
¹³ Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: j.a.h.zwart@medisin.uio.no.

PMID: 36640896
DOI: 10.1016/j.joca.2023.01.001

Abstract

Objectives: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain.

Methods: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations.

Results: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (β 0.07 (0.01-0.12)), and IL-6 (β -0.17 (-0.30 to -0.03)). Change in CXCL13 (β 2.43 (0.49-4.38)), CCL27 (β 3.07 (0.46-5.69)), IL-8 (β 1.83 (0.08-3.58)) and CCL19 (β 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups.

Conclusions: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored.

Keywords: Antibiotics; Cytokines; Inflammation; Low back pain; Modic changes.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Amoxicillin / therapeutic use
Anti-Bacterial Agents / therapeutic use
Chemokines
Chronic Pain* / drug therapy
Cytokines
Humans
Ligands
Low Back Pain* / drug therapy
Lumbar Vertebrae
Magnetic Resonance Imaging

Substances

Cytokines
Ligands
Amoxicillin
Anti-Bacterial Agents
Chemokines