Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury

James, Gregory, Sluka, Kathleen A., Blomster, Linda, Hall, Leanne, Schmid, Annina, Shu, Cindy C., Little, Christopher B., Melrose, James, and Hodges, Paul W. (2018) Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury. European Spine Journal, 27. pp. 1744-1756.

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Purpose: Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle.

Methods: Anterolateral lesions were induced at L3–4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals.

Results: A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased.

Conclusions: These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment.

Item ID: 72432
Item Type: Article (Research - C1)
ISSN: 1432-0932
Copyright Information: © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Program Grant ID631717, NHMRC Project Grant (APP1004032), NHMRC Senior Principal Research Fellowship APP1002190
Date Deposited: 20 Apr 2022 01:59
FoR Codes: 42 HEALTH SCIENCES > 4201 Allied health and rehabilitation science > 420106 Physiotherapy @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280112 Expanding knowledge in the health sciences @ 100%
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