SHIFT TOWARD T-LYMPHOCYTES WITH A T-HELPER-1 CYTOKINE-SECRETION PROFILE IN THE JOINTS OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To investigate whether T cells in the inflamed joints of pa tients with rheumatoid arthritis (RA) preferentially produce the T hel per 1 (Th1) cytokines, interferon-gamma (IFN gamma) and interleukin-2 (IL-2), or the Th2 cytokine, IL-4, when compared with corresponding pe ripheral blood-derived T cells. Methods. Synovial fluid mononuclear ce lls (SFMC) and corresponding peripheral blood mononuclear cells (PBMC) from 10 patients with RA were analyzed, either directly or after in v itro stimulation, for the intracellular presence of Th1 and Th2 cytoki nes. The amount of secreted cytokine in the cell culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). Results. IF N gamma-containing cells were detected in the unstimulated SFMC, but n ot in the PBMC, of 3 patients with RA, Cells positive for IL-2 or IL-4 were not detected in the unstimulated samples. Following stimulation, the mean percentage of cells containing Th1 cytokines was significant ly increased in the SFMC compared,vith the PBMC; no differences were f ound in the mean percentage of IL-4-containing cells, A comparable shi ft toward Th1 cytokines was observed when the amount of secreted cytok ine,vas determined by ELISA. Conclusion. A shift toward T cells with a Th1 cytokine profile was observed in the joints of patients with RA. Since an imbalance between Th1 and Th2 cells is thought to be of patho genic significance, this finding might have implications for the devel opment of new therapies for RA.