Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues.
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-gamma (IFNgamma) 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.


CONCLUSIONS
Greater IFNgamma 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.
Shamji
Mohammed F
MF
Duke University, Durham, North Carolina, USA. shamji@aya.yale.edu
Setton
Lori A
LA
Jarvis
Wingrove
W
So
Stephen
S
Chen
Jun
J
Jing
Liufang
L
Bullock
Robert
R
Isaacs
Robert E
RE
Brown
Christopher
C
Richardson
William J
WJ
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers; D016207:Cytokines; D020381:Interleukin-17