Positive feedback loop of interleukin-1β upregulating production of inflammatory mediators in human intervertebral disc cells in vitro

Object. Interleukin-1 beta (IL-1 beta) induces neurological symptoms in inter-vertebral disc herniation (IDH). Recently, the existence of a positive feedback loop of IL-1 beta, which encourages an inflammatory reaction or degeneration in the cells of tendon, has been reported. The authors hypothesized that there is a positive feedback loop of IL-1 beta in the cells of IDH. Methods. Eight human intervertebral disc specimens were harvested during spinal surgery for lumbar disc herniation. The cells were stimulated in serum-free medium with or without exogenous IL-1 beta. The messenger RNA (mRNA) was extracted for reverse-transcription polymerase chain reaction (PCR) and real-time PCR to quantify the mRNA of endogenous IL-1 beta, IL-6, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs). The cells were then stimulated in serum-free medium with or without exogenous IL-1 beta, and then exogenous IL-1 beta was removed. After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent assay was used to measure the protein concentration of endogenous IL-1 beta. The mRNA expressions of endogenous IL-1 beta, IL-6, COX-2, and MMPs were increased significantly depending on the concentration of exogenous IL-1 beta. The protein concentration of endogenous IL-1 beta was increased over time. Conclusions. There was a positive feedback loop of IL-1 beta in the cells of IDH. Furthermore, the productions of IL6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the increasing concentration of IL-1 beta in a positive feedback loop of IL-1 beta. The authors concluded that this positive feedback loop of IL-1 beta upregulated the production of mediators and thus can cause cessation of symptoms in IDH.