Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues

Abstract

Objective. Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue.Methods. Surgical IVD tissues were procured from patients with degenerative disc disease (n ‫؍‬ 25) or herniated IVDs (n ‫؍‬ 12); nondegenerated autopsy control tissue was also obtained (n ‫؍‬ 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions.Results. Immunoreactivity for IL-4, IL-6, IL-12, and interferon-␥ (IFN␥) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes.Conclusion. Greater IFN␥ positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration.

Human mesenchymal stem cell co-culture modulates the immunological properties of human intervertebral disc tissue fragments in vitro

“…The TNF-a decrease correlated with the reduction in IgG production and the PBLs' loss of proliferation, but both isoforms of IL-1 seem not to be implied in this regulation in a simple correlation. Unfortunately, we were not able to make a sound model of what is happening based on this data, because of the many unknowns, for instance other interleukins, which have not been analyzed here, have been associated with degenerated disc, such as IL-17 [6] and it is also known that the interleukins show pleiotropic effects, i.e. they have different targets in various cells and tissues.…”

“…The local production of matrix-degrading enzymes is a key event leading to degeneration, but it must be also considered in the context of the upstream molecules, such as cytokines, which regulate enzyme synthesis. IVD cells have a capacity to express a range of cytokines [6,7], including pro-inflammatory molecules, such as both isoforms of interleukin-1, alpha (IL-1a) and beta (IL-1b) [8] and tumor necrosis factor alpha (TNF-a) [9]. It has been proposed that IL-1 can regulate IVD cell expression of key matrixdegrading enzymes in vitro [10] and in vivo [11], placing this cytokine as a main factor inducing degeneration.…”

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

“…This supports the concept that treatment options targeting inflammatory factors or interleukins may be rather effective immediately after acute disc trauma but not at later stages of disc degeneration. Second, in the literature inflammatory mediators were mostly elevated in herniated or painful discs [25][26][27][28][29]. Hence, our gene expression data suggest that 6 months after disc injury, generalized painful disc inflammation was not apparent.…”

Low back pain: possibilities of pathogenetic treatment

“…В этом процессе участвуют различные секрети-руемые в МПД провоспалительные медиаторы: TNF-α, IL-1 α/β, IL-6, IL-17, IL-8, IL-2, IL-4, IL-10, IFN-γ, хемо-кины, простагландины (PGE2). Среди них TNF-α и IL-1 α/β являются наиболее изученными [19]. Эти цитокины стимулируют деградацию его матрикса, продукцию хемо-кинов, что приводит к изменениям клеточного фенотипа.…”