Serum cytokines in different histological variants of rheumatoid arthritis

Objective, Rheumatoid arthritis (RA) is characterized by an invasive and ti ssue destructive infiltrate of lymphocytes, macrophages, and synoviocytes f ormed in the joints. Its etiopathogenesis and the role of the particular mo rphological components of synovitis remain unclear. There is evidence that its histological heterogeneity is correlated with synovium cytokine transcr iption. We investigated whether the serum cytokine profile is associated wi th the morphological appearance of the disease. Methods. Tissue and serum samples were collected from 25 patients with clin ically active RA and 25 with osteoarthritis (OA) as a control group. After histological analysis RA synovial biopsies were divided into 2 distinct typ es; 16 samples were characterized by diffuse lymphocyte infiltrates with no additional microanatomical organization. Lymphocytic aggregates with germi nal center-like structures were found in 9 specimens. Serum concentrations of interferon-gamma (IFN-gamma), interleukin 12 (IL-12, p70 heterodimer), t umor necrosis factor (TNF-alpha), and IL-15 were measured by ELISA. Results. Low concentrations of IFN-gamma, (p < 0.01) and IL-12 (NS) were fo und in RA patients' serum compared with OA controls. RA patients with folli cular synovitis had lower serum concentration of IFN-gamma (p < 0.05) and I L-12 (p < 0.05) than patients with diffuse infiltrates. High concentration of TNF-alpha and IL-15 characterized RA patient serum in comparison with co ntrols (respectively, p < 0.001 and p < 0.01). In the serum of RA patients with follicular synovitis TNF-<alpha> was a dominant cytokine (p < 0.01) co mpared to patients with diffuse disease. At TNF-alpha level greater than or equal to 44 pg/ml, 5 (56%) of 9 patients with follicular RA had such eleva ted values vs one of 16 diffuse patients (< 10%; p < 0.02). Only serum conc entrations of TNF-alpha could effectively differentiate between patients wi th OA and subgroups of RA. Analysis of clinical data suggested that activit y of rheumatoid disease in patients with follicular synovitis was more seve re than in those with diffuse infiltrates. Conclusion. The association between distinct histological appearance of rhe umatoid synovitis and serum cytokine profile and diverse clinical activity of disease seems to confirm its heterogeneity.