Abstract

BackgroundOne of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. In the present study, correlations between proinflammatory cytokines in knee synovial fluid and radiographic changes and functional scores and pain scores among OA patients were examined.MethodsSynovial fluid was harvested from the knees of 47 consecutive OA patients, and the levels of TNFα, IL-6, and NGF were measured using enzyme-linked immunosorbent assays. Osteoarthritic knees were classified using Kellgren-Lawrence (KL) grading (1-4). The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness.ResultsTNFα and IL-6 were detectable in knee synovial, whereas NGF was not. TNFα was not correlated with the KL grade, whereas IL-6 had a significantly negative correlation. We observed differences in the correlations between TNFα and IL-6 with WOMAC scores and their subscales (pain, stiffness, and physical function). TNFα exhibited a significant correlation with the total score and its 3 subscales, whereas IL-6 exhibited a moderately significant negative correlation only with the subscale of stiffness.ConclusionsThe present study demonstrated that the concentrations of proinflammatory cytokines are correlated with KL grades and WOMAC scores in patients with knee OA. Although TNFα did not have a significant correlation with the radiographic grading, it was significantly associated with the WOMAC score. IL-6 had a significant negative correlation with the KL grading, whereas it had only a weakly significant correlation with the subscore of stiffness. The results suggest that these cytokines play a role in the pathogenesis of synovitis in osteoarthritic knees in different ways: TNFα is correlated with pain, whereas IL-6 is correlated with joint function.

Highlights

  • One of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFa), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA

  • We demonstrated that TNFa and IL-6 were detectable in the synovial fluid sampled from the knees of OA patients, whereas NGF was undetectable

  • The present study demonstrated that the concentrations of proinflammatory cytokines can be correlated with the KL grades and WOMAC scores of knee OA patients

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Summary

Introduction

One of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFa), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. The entire joint structure is affected, including the synovial production of inflammatory cytokines in the synovial membrane, such as tumor necrosis factor alpha (TNFa), interleukin (IL)-6, and nerve growth factor (NGF), which are generally considered to promote pathological OA [3,4,5]. IL-6 is reported to have a complex role in OA pathogenesis by initiating inflammatory responses such as the production of tissue inhibitors of metalloproteinase, and this may act to limit cartilage damage via negative feedback [8]. Another report indicated that NGF antagonism is an important mediator of pain in OA because its antagonistic effect resulted in analgesia in a murine OA model [10]

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