Background In vitro assays are widely used for characterisation of rheumatoid arthritis (RA) pathology and for testing of potential disease modifying anti-rheumatic drugs (DMARDs). However, little is known to what extent in vitro disease activity measures are correlated with in vivo disease activity.
Objectives The aim of this study was to investigate whether the release of interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1 beta (MIP-1b) correlated with serum c-reactive protein (CRP), tender joint count (TJC, 28 joints), swollen joint count (SJC, 28 joints) and disease activity score of 28 joints (DAS-28-CRP) of RA patients.
Methods Forty synovial sites from the hand joints of sixteen RA patients scheduled for biologic DMARD treatment were synovectomised by a needle-arthroscopic procedure. Synovial tissue was cultured for 72h, and the concentrations of IL-6, IL-8, MCP-1 and MIP-1b in the culture supernatants were measured by Multiplex immunoassays using heterophilic antibody blocking agents. Spearman rank correlations (r) were calculated for outcome measures using averaged values from the various explant positions. A p-value<0.05 was considered significant.
Results All four mediators were statistically significantly (least significant p-value =0.01) correlated with SJC (r=0.64, r=0.71, r=0.62 and r=0.65 for IL-6, IL-8, MCP-1 and MIP-1b, respectively). IL-6, IL-8 and MCP-1 were highly significantly correlated with TJC (r=0.78, 0.74 and r=0.77, respectively, p=0.001 for IL-8 and p=0.0004 for IL-6 and MCP-1, respectively), whereas MIP-1b had a lower correlation of r=0.58 (p=0.02) for TJC. IL-6 (r=0.58, p=0.02), IL-8 (r=0.56, p=0.03) and MCP-1 (r=0.70, p=0.003) were significantly correlated with DAS-28-CRP. In contrast no statistically significant correlation was found with DAS-28-CRP and MIP-1b (r=0.33, p=0.27) or any of the three mediators with CRP-levels.
Conclusions The production of pro-inflammatory mediators, IL-6, IL-8, MCP-1 and MIP-1b, by synovial explants from RA patients with active arthritis shows a high degree of correlation with clinical disease activity measures. This is indicative of a disease model that can facilitate translation of in vitro findings to in vivo effects.
Acknowledgements Supported by unrestricted grants from Novo Nordisk, The Danish Agency for Science Technology and Innovation and the Oak Foundation.
Disclosure of Interest M. Andersen: None declared, M. Boesen: None declared, K. Ellegaard: None declared, R. Christensen: None declared, K. Söderström Employee of: Nono Nordisk, N. Søe: None declared, P. Spee Employee of: Nono Nordisk, U. Mørch Shareholder of: Nono Nordisk, Employee of: Nono Nordisk, S. Torp-Pedersen: None declared, E. Bartels: None declared, B. Danneskiold-Samsøe: None declared, N. Vendel: None declared, L. Karlsson Employee of: Nono Nordisk, H. Bliddal Grant/research support: Nono Nordisk