Relationships between local inflammation, interleukin‐6 concentration and the acute phase protein response in arthritis patients

Abstract

Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors.

Arthritis of the large joints--in particular, the knee--at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis

“…Holt et al previously showed that, in patients with inflammatory arthritis, the concentration of synovial interleukin-6 in knee joints was associated with the plasma level of interleukin-6 and also with plasma level of CRP. 25 In experimental studies in rabbits, interleukin-1b infusion by intraarticular knee injection with a retroviral vector containing a DNA fragment encoding for mature interleukin-1b 26 27 yielded not only a local reaction in the knee resembling human RA with the formation of pannus and bony erosions, but also a dramatic systemic response with severe systemic manifestations. These findings also support the notion that the presence of a large area of inflamed synovium (ie, involvement of a large joint as the knee) is correlated with higher systemic level of proinflammatory cytokines and a more severe disease outcome.…”

Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma

“…Pheochromocytoma and liposarcoma are examples of IL-6-producing tumours with associated thrombocytosis (Nagasawa et al, 1990;Suzuki et al, 1991). In some other diseases, such as rheumatoid arthritis and cardiac myxoma, and in burmed patients, the elevation of serum IL-6 levels has also been demonstrated (Holt et al, 1991;Jourdan et al, 1991;Nijsten et al, 1991).…”

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

“…Raised levels of proinflammatory cytokines have been reported in the progression and complications associated with other inflammatory or immune conditions such as myocarditis and cardiac failure (Heymans et al, 2009;Watanabe et al, 2011;Gullestad et al, 2012;Cialdella et al, 2013), chronic kidney disease (Stenvinkel et al, 2005;Carrero et al, 2008Carrero et al, , 2009Filiopoulos and Vlassopoulos, 2009;Rosner et al, 2012), diabetes (Pickup et al, 2000;de Galan et al, 2003;Tuttle et al, 2004;Konukoglu et al, 2006), and rheumatoid arthritis (Holt et al, 1991;Feldmann, 1996;Vervoordeldonk and Tak, 2002). Because raised levels of certain cytokines down-regulate certain DMEs, it seems reasonable to anticipate that drug metabolism may also be down-regulated in many of these widely prevalent inflammatory conditions, potentially giving rise to phenoconversion and genotype-phenotype mismatch, often reflected as unexpected and otherwise unexplained increases in plasma concentrations of the parent drug.…”