Elevated levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury

Abstract

BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild ( n = 20), moderate ( n = 19) and severe ( n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury ( P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity ( P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.

Mechanisms of vascular invasion after cartilage injury and potential engineering cartilage treatment strategies

“…The macrophage phenotype accumulates and localizes after articular cartilage injury. Macrophages, fibroblasts and chondrocytes secrete increased inflammatory factors, including interleukin‐1ß( IL‐1ß ), IL‐6 , IL‐8 , IL‐17 , IL‐18 , tumor necrosis factor‐ɑ ( TNF‐ɑ ), etc 86,87 . These inflammatory factors can directly or indirectly activate some signaling pathways related to angiogenesis, such as STAT3 , NF‐κB , PI3K/Akt , and p38 MAPK .…”

A roadmap to target interleukin-6 in osteoarthritis

“…Moreover, a high innate capacity to produce IL-6, in response to lipopolysaccharide stimulation, was associated with hand OA development in 90-year-old individuals [ 45 ]. Higher IL-6 levels in OA serum or SF also correlate with disease progression or severity of cartilage pathology [ 42 , 46–48 ]. This suggests that IL-6 levels may reflect cartilage damage, which is supported by the fact that SF IL-6 levels are strongly increased in individuals with cartilage defects but no macroscopic signs of OA [ 49 , 50 ].…”

Silk-based hydrogel incorporated with metal-organic framework nanozymes for enhanced osteochondral regeneration

“…The onset of defects affects the microenvironment of the whole joint [ 4 , 5 ]. After OCD, an acute inflammatory response occurs in the joint [ 6 , 7 ]. Previous studies have identified the overexpression of interleukin-1β (IL-1β) in the surrounding tissues of the defect [ 8 , 9 ].…”

“…After OCD, an acute inflammatory response occurs in the joint [ 6 , 7 ]. Previous studies have identified the overexpression of interleukin-1β (IL-1β) in the surrounding tissues of the defect [ 8 , 9 ]. The local inflammatory microenvironment has been proved to be a barrier to osteogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs) [ [10] , [11] , [12] ].…”