A New Understanding of the Role of IL-1 in Age-Related Intervertebral Disc Degeneration in a Murine Model.

Increased cytokine expression, in particular interleukin-1β (IL-1β), is considered a hallmark of intervertebral disc degeneration. However, the causative relationship between IL-1 and age-dependent degeneration has not been established. To investigate the role of IL-1 in driving age-related disc degeneration, we studied the spine phenotype of global IL-1α/β double knockout (IL-1KO) mice at 12 and 20 months. Multiplex ELISA analysis of blood revealed significant reductions in the concentrations of IFN-γ, IL-5, IL-15, TNF-α, IP-10, and a trend of reduced concentrations of IL-10, macrophage inflammatory protein 1α (MIP-1α), keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and IL-6. However, the circulating level of MIP-2, a neutrophil chemoattractant, was increased in the IL-1KO. The alterations in systemic cytokine levels coincided with altered bone morphology-IL-1KO mice exhibited significantly thicker caudal cortical bone at 12 and 20 months. Despite these systemic inflammatory and bony changes, IL-1 deletion only minimally affected disc health. Both wild-type (WT) and IL-1KO mice showed age-dependent disc degeneration. Unexpectedly, rather than protecting the animals from degeneration, the aging phenotype was more pronounced in IL-1KO animals: knockout mice evidenced significantly more degenerative changes in the annulus fibrosis (AF) together with alterations in collagen type and maturity. At 20 months, there were no changes in nucleus pulposus (NP) extracellular matrix composition or cellular marker expression; however, the IL-1KO NP cells occupied a smaller proportion of the NP compartment that those of WT controls. Taken together, these results show that IL-1 deletion altered the systemic inflammatory environment and vertebral bone morphology. However, instead of protecting discs from age-related disc degeneration, global IL-1 deletion amplified the degenerative phenotype. © 2019 American Society for Bone and Mineral Research.