Inflammatory Cytokines in the Herniated Disc of the Lumbar Spine

Takahashi, Hiroshi; Suguro, Toru; Okazima, Yukikazu; Motegi, Mituo; Okada, Yayoi; Kakiuchi, Terutaka

doi:10.1097/00007632-199601150-00011

Cited by 476 publications

(240 citation statements)

References 28 publications

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“…The (PI3K)-Akt pathway mediates inflammatory responses, while the activation of Akt/PKB has been implicated in macrophage phagocytosis of foreign bodies [22,23]. Our hypothesis is reinforced by the findings of Shiratsuchi and Basson who report that changes in tissue pressure during inflammation may regulate macrophage phagocytosis by the activation of PI-3K/Akt2/PKBb, but not Akt1/PKBa and Akt3/PKBc [24].…”

Section: Duration Of Symptomssupporting

confidence: 62%

Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings

et al. 2011

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Intervertebral disc (IVD) degeneration suggests a complex process influenced by genetics, lifestyle and biomechanics, which accounts for the development of low back pain (LBP) and lumbar radiculopathy, a major cause of musculoskeletal disability in humans. The family of Akt/ PKB kinases is a principal mediator in the signal transduction pathways, which contribute to transcriptional regulation, cell growth, proliferation, apoptosis, and survival ability. The purpose of this study was to evaluate the transcriptional profile of the AKT family genes in human herniated discs and the involvement of the PI3K-Akt signaling pathway in human IVD degeneration. Real-time PCR analysis was used to assess the mRNA expression pattern of the three Akt/PKB isoforms in 63 herniated and 10 control disc specimens. Our results showed a significant positive correlation between AKT1 and AKT3 mRNA in herniated discs suggesting a synergistic action between these isoforms in disc herniation. Interestingly, AKT2 mRNA was up-regulated in patients with acute pain during the first 12 months, indicating that AKT2 transcriptional activation may be associated with acute rather than chronic inflammation and phagocytosis. Finally, Akt1/PKB transcription presented a stepwise activation as disc herniation deteriorated. Our findings provide evidence on the transcriptional activation of the Akt/PKB pathway indicating that it is involved in lumbar disc degeneration. There is need for further studies to elucidate the exact role and down-stream signaling action of Akt/PKB isoforms in the pathogenesis of lumbar disc herniation.

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Section: Duration Of Symptomssupporting

confidence: 62%

Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings

et al. 2011

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“…Previous reports showed proinflammatory cytokines such as IL-1b, IL-6, and TNF were expressed in human herniated disk specimens [8,28]. Intervertebral disk cells may produce TNF-a, IL-1b, and monocyte chemoattractant protein-1 immediately after the onset of disk herniation [32].…”

Section: Discussionmentioning

confidence: 96%

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

et al. 2009

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There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders. This study investigated whether interleukin-1b (IL-1b), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a) could be detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines correlated with the severity of disease conditions. CSF samples were obtained from 21 patients with cervical myelopathy (Group M) and 19 patients with lumbar radiculopathy (Group R), and six volunteers (control). The concentration of IL-6 was significantly higher in Groups M and R than in the control, possibly demonstrating spinal cord and nerve root damage, respectively. However, TNF-a was lower than the detection limit. IL-1b was detected in only five samples from three patients in Group M and two volunteers in the control. The concentrations of IL-6 did not show any correlation with symptom duration, the scoring system by the Japanese Orthopaedic Association, or the duration of nerve root block. There is a possibility that the concentration of inflammatory cytokines in CSF can indicate certain pathological aspects of cervical myelopathy or lumbar radiculopathy.

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“…Nevertheless, the data reported here provide a theoretical basis for further research. Second, cells in degenerated intervertebral disc tissues are composed of heterogeneous cell types, such as macrophages [31], and the Passage 0 culture is not pure, although macrophages are suspension 1, 10, and 100 ng/mL) for 12 hours, lipopolysaccharide increased MIF expression in a dose-dependent manner as assessed by ELISA. Data are presented as mean ± SD.…”

Section: Discussionmentioning

confidence: 99%

Migration Inhibitory Factor Enhances Inflammation via CD74 in Cartilage End Plates with Modic Type 1 Changes on MRI

Xiong

Huang

Cun

et al. 2014

Clinical Orthopaedics &Amp; Related Research

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Background Type 1 Modic changes are characterized by edema, vascularization, and inflammation, which lead to intervertebral disc degeneration. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine closely related to the inflammatory cytokines detected in degenerative intervertebral disc tissues. However, the existence and role of MIF and its receptor CD74 in intervertebral disc degeneration have not been elucidated. Questions/purposes We asked whether (1) MIF and its receptor CD74 are expressed in cartilage end plates with Type 1 Modic changes, (2) MIF is associated with cartilage end plate degeneration, (3) the MIF antagonist (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) suppresses MIF-induced inflammatory cytokine release, and (4) inflammatory cytokines are released by cartilage end plate chondrocytes via CD74 by activating the CD74 antibody (CD74Ab). Methods We examined MIF and CD74 expression by human cartilage end plate chondrocytes and tissues with Type 1 Modic changes from eight patients using immunocytofluorescence and immunohistochemistry. MIF production by the chondrocytes was assessed by ELISA and PCR. We compared cytokine release by chondrocytes treated with MIF in the presence or absence of exogenous ISO-1 by ELISA. Cytokine release by chondrocytes after treatment with CD74Ab was determined by ELISA. Results MIF was expressed in degenerated human cartilage end plate tissues and chondrocytes. Lipopolysaccharide and tumor necrosis factor a (TNF-a) upregulated MIF expression and increased MIF secretion in chondrocytes in a dose-dependent manner. MIF increased the secretion of IL-6, IL-8, and prostaglandin E2 (PGE2) in a dose-dependent manner. ISO-1 reduced the secretion of IL-6, IL-8, and PGE2. CD74Ab activated CD74 and induced release of inflammatory cytokines. Conclusions Chondrocytes in cartilage end plate with Type 1 Modic changes express MIF and its receptor CD74.

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Inflammatory Cytokines in the Herniated Disc of the Lumbar Spine

Abstract: The results demonstrate that at the site of lumbar disc herniation, inflammatory cytokines such as interleukin-1 alpha are produced, which increases prostaglandin E2 production. Further studies are required to elucidate the role of inflammatory cytokines in causing sciatic pain.

Cited by 476 publications

References 28 publications

Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings

Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings

Tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy

Migration Inhibitory Factor Enhances Inflammation via CD74 in Cartilage End Plates with Modic Type 1 Changes on MRI

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