Immunomorphogenesis in degenerative disc disease: the role of proinflammatory cytokines and angiogenesis factors

Abstract

ABSTRACTBack pain (BP) due to degenerative spinal injury is a severe, often disabling disease and it tends to decrease age of onset. The cellular and molecular basis of the disc and adjacent structures degradation remains in the focus of pathophysiologists and pathomorphologists close attention. The aim of the study was to determine the expression level of proinflammatory cytokines (IL-1β, IL-6, IL-17) and angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue, their association between each other and between disc degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging (MRI) of the lumbar spine, histological and immunohistochemical analyses of these factors in the disc tissue were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the degenerative disc disease (DDD) group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant expression of IL-1β, IL-6, IL-17 and VEGF-A (especially on the chondrocytes surface) and CD31 (in the disc matrix) was evident in the samples of the DDD group compared with the controls (p < 0.0001), that showed a strong correlation with the histological disc degeneration stage (r > 0.5; p < 0.0001). This denotes a high immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties. The coincidence of the spatial expression of IL-1β and IL-17 in the perivascular zone endothelium and in the vascular lumen (p < 0.01) was found, which point at the inflammatory synergy of these cytokines. High expression of VEGF-A prevailed on the surface of chondrocytes in cell clusters compared to the matrix (p < 0.0001), indicating that the NP cells trigger the angiogenesis. The absence of CD31 in the cracks of NP with high expression in the disc matrix states the secondary nature of IVD defects due to degeneration, and not due to vascular ingrowth. A high number of patients with Modic changes according to MRI data shown the contribution of cytokines to the formation of reactive spondylitis and the clinical course of BP. These results obtained will help to development molecular/cellular targets and basic strategies for therapy of BP with DDD in the early stages in young people.