Interleukin-2 Secretion by Synovial Fluid Lymphocytes in Rheumatoid Arthritis

Abstract

Interleukin-2 (IL-2) receptor bearing cells and soluble IL-2, measured in a bioassay with IL-2 dependent human T-cell blasts, were recognized in synovial fluid, but not in the peripheral blood of patients with rheumatoid arthritis (RA). After stimulation in vitro with appropriate concentrations of the mitogen concanavalin A (Con-A), comparable proportions of IL-2 receptor (IL-2R) bearing cells were seen in cultures of synovial fluid lymphocytes (SFL) and in cultures of peripheral blood lymphocytes (PBL). On the other hand, higher levels of secreted IL-2 were found in SFL cultures compared to corresponding PBL cultures of RA patients and normal donors. Specificity of the IL-2 bioassay was confirmed by blocking the T-cell blast proliferation (induced by SFL culture supernatants), by 83 +/- 4%, after addition of a monoclonal anti-IL-2R antibody. Despite the high levels of soluble IL-2, only a weak proliferative response was observed in the corresponding SFL cultures.

Selective inhibition of interleukin‐1β gene expression in activated RAW 264.7 macrophages by interferon‐γ

“…Although our observations are in agreement with some reports [12,28,291, they are inconsistent with other reports which indicate that IFN-y actually potentiates LPS-stimulated accumulation of steady-state lL-1p mRNA levels in human PBMC [lo, 11, 30, 311 and in synovial fluid mononuclear leukocytes [12]. The reason for the apparent discrepancy is not clear.…”

“…IFN-y, which per se does not stimulate macrophages to produce IL-lP in LPS-free culture medium, has been repeatedly shown to amplify the production of the cytokine by LPS-stimulated macrophages [lo-121 and LPS-stimulated human neutrophils [13]. In contrast, several reports show that IFN-y can selectively inhibit the LPS-stimulated IL-1p production by synovial fluid mononuclear cells [12] and IL-l-induced IL-1 synthesis in human PBMC [lo, 111. The beneficial effects of IFN-y seen in certain chronic inflammatory conditions including rheumatoid arthritis [16][17][18] and its antiinflammatory activity observed against LPS-induced local inflammation [19] suggest that IFN-y cannot be regarded only as a macrophage-activating agent.…”

Effector Functions of CD4+ T Cells at the Site of Local Autoimmune Inflammation—Lessons From Rheumatoid Arthritis

“…Regulatory T cells from peripheral blood and inflamed joints of juvenile arthritis patients were shown to harbor a different T cell Receptor Vβ usage than conventional T cells suggesting that Tregs would be generated independently of conventional T cells (140). Whether this is also the case in RA is currently unknown but IL-2 (141) and TGFβ (142), important for induced regulatory T-cell generation are present in synovial fluids of RA.…”

“…IL-2 and IL-15 as well as 4-1BB triggering are thought to favor their generation (160). Importantly, IL-2 (141) and IL-15 (175) are present in synovial fluids of RA patients while soluble forms of 4-1BB and 4-1BB ligand are increased in peripheral blood of RA patients (176). The functional implications of CD4+ CTLs interactions with HLA class-II expressing cells in synovial joints such as macrophages, dendritic cells, neutrophils (177), chondrocytes (178), or endothelial cells remains largely unknown.…”

Cytokine regulation of human monocyte interleukin-1 (IL-1) productionin vitro. Enhancement of IL-1 production by interferon (IFN) gamma, tumour necrosis factor-alpha, IL-2 and IL-1, and inhibition by IFN-alpha

“…IL-1, IL-2, TNF-cx, IFN-y and IFN-cx have all been identified in inflamed rheumatoid joints (Hopkins & Meager, 1988;Ruschen, Lemm & Warnatz, 1988; Giovine, Nuki & Duff, 1988;Buchan et al, 1988). It is possible that some ofthese cytokines, even ifpresent in relatively low amounts, may serve to enhance the production of IL-1 which is presumed responsible for much of the tissue destruction.…”