Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine

Abstract

IntroductionThe pathogenetic mechanism of low back pain and nerve root damage in lumbar disc herniation is the subject of ongoing debate. In particular, given that the mechanicalischaemic hypothesis alone cannot explain the cause-effect relationship between disc degeneration and neurological impairment, a biochemical mechanism is likely to be involved. It has recently been demonstrated that the autologous nucleus pulposus can induce histological and functional changes in spinal nerve roots when applied epidurally [17]. Cells of the nucleus pulposus can produce prostaglandin E2, interleukin-1 and interleukin-6 (IL-6) [31], phospholipase A2 [26], and growth factors like fibroblast-like growth factor (FGF) [32] and insulin-like growth factor-1 (IGF-1) [18]. These factors are known to control cell metabolism and to promote inflammatory processes. Moreover, recent studies suggest a critical role for IL-6 and its receptor in the modulation of pain [8]. The mechanisms of action underlying the possible effect of these factors on spinal nerve root structure and function are, however, still unknown. In addition, the fact that nerve roots differ from peripheral nerves in their anatomical, biomechanical, and physiological properties prevents extrapolation from the extensive literature and the numerous experimental models of peripheral nerve compression to the pathophysiology of root injury [5,23,25]. The working hypothesis of the present study is that transforming growth factor-β1 (TGF-β1), IGF-1, IL-6 and IL-6-receptor (IL-6R) can be produced at the site of herniation. This hypothesis was immunohistochemically explored by analysing normal and protruded intervertebral disc tissue for these factors.Abstract Nerve root irritation induced by factors produced by the intervertebral disc may play a crucial role in the pathophysiology of sciatic pain production. In this study we used immunohistochemistry to investigate the presence of transforming growth factor-β1 (TGF-β1), insulinlike growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc bioptic specimens from 30 patients with disc herniation (protrusion type). Chondrocytes of herniated discs stained positive for TGF-β1, IGF-1, IL-6 and fibronectin. We demonstrated for the first time the presence of IL-6-R in the chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were used as controls. In these sections no immunoreaction for TGF-β1, IL-6, or IL-6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities than herniated discs. These results demonstrated the production of factors such as TGF-β1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc herniation.

Text-mining network analysis of the response to osmotic stimuli in the intervertebral disc

“…IL-6 has multiple functions in a wide variety of biological processes, including the immune system, neuronal regulation, hematopoiesis, and inflammation (Gadient and Otten, 1997;Barnes et al, 2011). Relevant to this study are the findings that a protruded IVD was immunoreactive for IL-6 at a 4-fold higher intensity than normal tissue (Specchia et al, 2002). Therefore, this cytokine may have an important, but unknown, function in regulating cell function in IVD pathology.…”

Serum cytokine levels in patients with chronic low back pain due to herniated disc: analytical cross-sectional study

“…The increased concentrations of these substances in the herniated disc tissue suggests that cytokines potentially have the ability to cause endoneural edema and nerve fiber demyelination. [21][22][23] Furthermore, cytokines excite nociceptors, which suggests that they may play a critical role in peripheral hyperalgesia and pain behavior. 24,25 Nonetheless, the potential involvement of these substances in disc herniation may be related to a local process.…”

Growth factor expression in degenerated intervertebral disc tissue

“…Some studies have suggested that this growth factor is absent in control disc tissue [7,23]. However, in a recent biochemical tissue culture study on growth factors and inflammatory mediators in patients undergoing surgery for scoliosis, lumbar radiculopathy and discogenic pain, production of TGFb-1 was demonstrated both in control (scoliosis) and degenerate human disc tissues [2].…”