Expression and Relationship of Proinflammatory Chemokine RANTES/CCL5 and Cytokine IL-1β in Painful Human Intervertebral Discs

Study Design. Laboratory study. Objective. To evaluate expression of chemokine regulated and normal T cell expressed and secreted (RANTES)/C-C motif ligand 5 (CCL5) and interleukins in intervertebral discs (IVDs) specimens from patients with discogram-proven painful degeneration. Summary of Background Data. Discogenic back pain results in tremendous costs related to treatment and lost productivity. The relationship between inflammation, degeneration (IVD), and cytokine upregulation is well established, but other mediators of the infl ammatory cascade are not well characterized. Methods. Painful IVDs were taken from 18 patients undergoing surgery for discogenic pain with positive preoperative discogram. Painless control tissue was taken at autopsy from patients without back pain/spinal pathology or spinal levels with negative discograms resected for deformity. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to evaluate RANTES, IL-1 beta, IL-6, and IL-8 expression in painful and control discs. RANTES and interleukin expression were analyzed on the basis of Pfirrmann grade. Disc cells were cultured in alginate beads using 2 groups: an untreated group and a group treated with 10 ng/mL IL-1 beta, 10 ng/mL TNF-alpha, and 1% fetal bovine serum to induce a degenerative phenotype. Results. Nine painless IVD specimens and 7 painful IVD specimens were collected. RANTES expression demonstrated a 3.60-fold increase in painful discs versus painless discs, a significant difference (P = 0.049). IL-1 beta expression demonstrated significantly higher expression in painful discs (P = 0.03). RANTES expression data demonstrated significant upregulation with increasing Pfirrmann grade (P = 0.045). RANTES expression correlated significantly with IL-1 beta expression (rho = 0.67, P < 0.0001). RANTES expression increased more than 200-fold in the alginate culture model in cells treated with IL-1 beta/TNF-alpha, 1% fetal bovine serum (P < 0.001). Conclusion. RANTES and IL-1 beta expression was significantly elevated in painful IVDs after careful selection of painless versus painful IVD tissue. RANTES expression was found to correlate significantly with expression of IL-1 beta. RANTES was upregulated by IL-1 beta/TNF-beta/1% fetal bovine serum an in vitro treatment to induce a degenerative phenotype.