STUDY DESIGN: Case-control study. OBJECTIVE: To determine whether inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-8] are elevated in tissues intimately surrounding involved nerve roots of patients suffering from radiculopathy form herniated disc (HD). SUMMARY OF BACKGROUND DATA: Proinflammatory cytokines are postulated to play an important role in radiculopathy from HD. Although TNF-alpha has been found in human HD, it is not known whether TNF-alpha concentrations are increased in symptomatic patients. Epidural fat (EF) is another tissue in close contact with nerve roots. Histologic modifications of EF have been reported in patients with sciatica but concentrations of inflammatory cytokines have never been studied. METHODS: Twenty-three lumbar HD along with adjacent EF (EFHD) were harvested from patients with radicular syndrome. As controls, 14 intervertebral discs (IVDs) and 10 samples of EF (EFC) were obtained from patients without radicular syndrome undergoing spine surgery. Tissue explants were incubated ex vivo for 48 hours and the concentrations of cytokines were measured by elisa in the supernatants. Results were standardized according to tissue weight. RESULTS: All 4 cytokines were found at higher concentrations in EFHD compared with HD (P < 0.001). TNF-alpha was the only cytokine found in significantly higher levels in EFHD compared with EFC [median, interquartile range 6.6, (1.6-16.3) pg/mL per milligram of tissue vs. 2.3 (1.3-5.0), P < 0.05] and to subcutaneous fat [0.35 (0-2.28), P < 0.001]. No significant increase of either cytokines was found in HD compared with IVD. CONCLUSION: Higher concentrations of TNF-alpha were found in EF from patients with radiculopathy from HD compared with patients suffering from other type of back pain. These results support the role of TNF-alpha in the pathogenesis of radiculopathy from HD.