Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis

Objectdive. We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM‐1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM‐1 originates from the synovium. Methods. Circulating ICAM‐1 (cICAM‐1) levels were determined by sandwich enzyme‐linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM‐1 was assessed by overnight incubation at 37°C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM‐1 with patient synovial fluid. Results. RA sera contained significantly greater (P < 0.001) levels of cICAM‐1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM‐1 levels were unaffected by overnight incubation at 37°C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM‐1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs. Conclusion. The greatest elevations of cICAM‐1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM‐1 levels were consistently lower than serum levels, suggesting that cICAM‐1 did not originate in the synovium. Because the production of cICAM‐1 can be increased by cytokines (e.g., interleukin‐1, tumor necrosis factor α), elevated levels of circulating ICAM‐1 in RA may be reflective of systemic exposure to elevated cytokine levels.