Abstract
Spontaneous degeneration of an intervertebral disc is caused by inflammation that accompanies exposure of the avascular nucleus pulposus to circulation, triggering an autoimmune inflammatory reaction. Both intrinsic and extrinsic mechanisms of IVD regulation by various cytokines are involved in disc degeneration and spontaneous hernia resorption through inflammatory responses. The major goal of this narrative review was to assemble our past findings about the potential role of cytokines in disc diseases and to clarify directions for future research. A member of the tumor necrosis factor-α (TNF-α) superfamily, TNF-like weak inducer of apoptosis (TWEAK) is constitutively expressed in the intervertebral disc, and induces a chronic, but relatively weak inflammatory response, thereby suppressing the formation of cartilage matrix and inducing production of matrix metalloproteinases (MMPs). Previously we indicated that TWEAK is involved in intervertebral disc degeneration by inhibiting the production of cartilage matrix in the intervertebral disc, and inducing the further expression of MMP-3. Thymic stromal lymphopoietin (TSLP) is expressed primarily by epithelial cells, and induces inflammation at the time of tolerance failure in allergic disease. We found TSLP induced migration of immunocompetent cells to the disc in intervertebral disc disease by promoting the production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1α) by the intervertebral disc and these cells may be involved in the resorption of herniated disc tissue. Considering the pivotal role of TWEAK and TSLP we review our current understanding of these factors and their involvement in disc degeneration.