PRODUCTION OF T-CELL CYTOKINES AT THE SINGLE-CELL LEVEL IN PATIENTS WITH INFLAMMATORY ARTHRITIDES - ENHANCED ACTIVITY IN SYNOVIAL-FLUID COMPARED TO BLOOD

We used a newly developed, sensitive ELISPOT technique in order to est imate the number of cells producing interferon-gamma (IFN-gamma) and i nterleukin-4 (IL-4) in synovial fluid mononuclear cells (SFMC) and per ipheral blood mononuclear cells (PBMC) in patients with rheumatoid art hritis (RA) and other inflammatory arthritides, and to correlate the r esults with clinical and laboratory parameters of disease activity. SF MC and PBMC were cultured either without stimuli or with a standardize d dose of phytohaemagglutinin (PHA) for 6 h. Twenty-nine patients, 16 with RA and 13 with other inflammatory joint diseases, were investigat ed and compared to PBMC from 25 healthy controls. The mean number of I FN-gamma-producing cells was 37.1/10(5) plated SFMC (range 0-121.5). T he corresponding value for PBMC was 5.1 (0-39). The difference was hig hly significant (P = 0.0033 for RA patients, P = 0.0050 for non-RA pat ients and P < 0.0001 for all patients). Forty-five per cent of SFMC sa mples (range for all samples 0-38.5 SFC/10(5) MNC) and 25% of PBMC sam ples (0-20.5) exhibited spontaneous IL-4 production, yielding a signif icant difference for all patients treated collectively (P = 0.021). Al though the cells that spontaneously secrete these cytokines are relati vely few, quantification of these cells thus shows increased functiona l T-cell activation and decreased ratio of cells spontaneously produci ng IL-4 vs IFN-gamma in the joint fluid as compared to blood of arthri tis patients.