RESTRICTED CYTOKINE EXPRESSION IN RHEUMATOID-ARTHRITIS

Objective. To determine the cytokine profile of the phenotypically activated T cell in rheumatoid arthritis (RA) synovium. Methods. Interleukin-2 (IL-2), IL-2 receptor (IL-2R), IL-6, IL-4, and interferon-gamma (IFNgamma) gene expression was examined in T cells from freshly isolated synovial fluids (SF) and synovial tissues (ST) from patients with RA. Estimates of baseline expression were determined using unstimulated peripheral blood (PB) T cells from healthy individuals. The corresponding positive controls were phytohemagglutinin-activated tonsil T cells. Results. In studies of paired PB and SF T cell samples from 17 RA patients, IL-2 messenger RNA (mRNA) levels in only 1 PB and 3 SF samples were more than 2 standard deviations above the mean of levels in unstimulated PB from healthy donors. Similarly, only 5 PB and 7 SF samples exhibited elevated IL-2R mRNA levels. IFNgamma gene expression was not detected in any of the paired RA PB or SF samples. Fractionated T cells from 12 RA ST were screened with similar results: Only 1 of 12 samples exhibited IL-2 mRNA levels more than 2 standard deviations above levels in baseline controls. IL-2R mRNA levels were low or not detected, and IFNgamma mRNA was absent. Subsequent studies showed that IL-4 and IL-6 gene expression levels were also low in RA tissues compared with tonsil T cell-positive controls. Conclusion. These data provide evidence for restricted cytokine expression in the T cell population in RA tissues.