Potential Therapies for Intervertebral Disk Disease: The Role of Cytokine Pathways

Kevin Deane, MD


August 16, 2010

Proinflammatory Cytokine Expression Profile in Degenerated and Herniated Human Intervertebral Disk Tissues

Shamji MF, Setton LA, Jarvis W, et al
Arthritis Rheum. 2010;62:1974-1982


Back pain due to disk degeneration (acute or chronic) causes significant disability. Investigations to understand the underlying etiology of this disk degeneration, and ultimately to decrease morbidity from it, are welcome. Recently, intriguing data suggest that inflammation may figure prominently in disk disease, with studies of disk tissue demonstrating increased inflammatory molecules that may be related to T helper cell 1 (Th1) lymphocyte differentiation, including interleukin (IL)-6, tumor necrosis factor-alpha, and interferon-gamma (IFN-γ).[1] Shamji and colleagues further investigated the role of Th1, as well as Th17-mediated inflammation, in intervertebral disk (IVD) disease by examining the presence of IL-17 in patients with degenerative or herniated disk disease compared with autopsy controls.

Study Summary

Intervertebral disk tissue was obtained from 35 patients undergoing surgery for chronic degenerative disease (n = 25) or an acutely herniated disk (n = 12). Of note, 48% of patients with degenerative disk disease and 92% of patients with herniated disks had undergone epidural steroid injection, but the use of oral corticosteroids was unknown in these patients. Intervertebral disk tissue was also obtained from 4 cadavers who did not have grossly degenerative disk disease. Tissues were examined for cellularity and cytokines. Compared with control tissue, degenerative and herniated IVD tissue had higher levels of IL-4, IL-6, IL-12, IL-17 and IFN-γ; increased macrophages; and modestly increased lymphocytes. A greater number of macrophages, as well as increased IFN-γ and IL-6 levels, were in herniated vs degenerative disk tissue. The authors conclude that these results suggest involvement of Th1 and Th17 pathways in the pathogenesis of disk disease.


Identifying inflammatory pathways in the evolution of disk disease is important, because such findings may lead to therapeutic interventions. The finding of increased Th1 and Th17 markers in disk disease compared with cadaver controls is of interest in terms of the pathogenesis of disease and may lead to beneficial therapies. However, the ultimate contribution of this cytokine to the pathogenesis of disk disease is difficult to determine because proinflammatory cytokines may be present in a variety of tissue injuries and may not be specific for disk disease. It would be interesting to compare disk findings from these surgical samples with those from cadavers with IVD disease (degenerative or disk rupture) but no history of surgery, or damaged tissue obtained from routine hip and knee replacements for osteoarthritis. As a take-home point, this study should remind us that inflammatory pathways may be present in many diseases previously thought to be primary mechanical; however, we need more data before the true significance of the Th1 and Th17 pathways in disk disease can be understood.



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