Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis

We attempted to determine whether various cytokine levels in the serum and synovial fluid (SF) of rheumatoid arthritis (RA) patients are influenced by the performance of filtration leukocytapheresis (LCP). The filtration LCP procedure that used a Cellsorba (R) column (LCP group: n = 22; responder subgroup: n = 17, non-responder sub.-roup: n = 5) or sham apheresis (control group; n = 7) was repeated three times at 1-week intervals. Serum (LCP group, n = 22; control group, n = 7) and SF (LCP group, n = 6 control group, n = 3) samples were collected before and after LCP. Levels of tumor necrosis factor alpha (TNF alpha), interleukins (IL-1 beta, IL-2, IL-6, IL-8, IL-10, and IL-15), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), RANTES were measured by an enzyme-linked immunosorbent assay. Serum TNF alpha, IL-15, and RANTES were significantly reduced only in the LCP group. Serum LL-10 significantly increased only in the LCP group. In the LCP subgroup, serum IL-15. GM-CSF. and RANTES levels were reduced significantly, while serum IL-10 levels increased significantly only in the responder group after treatment. Serum TNF alpha levels were reduced significantly in both ubgroups. Changes in serum IL-10 correlated positively with the improvement of patient's assessment of pain and global severity, and physician's assessment of global severity. These results indicate that the removal of leukocytes from the peripheral blood of RA patients provokes dynamic changes in some cytokine levels in the serum and/or synovial fluid. These changes may explain some of the mechanisms by which the articular symptoms are improved by filtration LCP. J. Clin. Apheresis. 16:74-81, 2001. (C) 2001 Wiley-Liss, Inc.