Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury
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.
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.
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.
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.
KeywordsMacrophage Multifidus muscle IVD lesion Pro-inflammatory TNF Adipose
PWH has a Senior Principal Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1002190). The study was funded by a NHMRC Program Grant (ID631717) and Project Grant (APP1004032). The funding source did not play a role in investigation.
Compliance with ethical standards
Conflict of interest
Outside of this study, Kathleen A. Sluka recieved research funding from Medtronic, Inc, consultancy fees from Bayer Inc. and a book honorarium from IASP Press. The other authors declare they have no conflicts of interest.
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