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Plasma levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean 2 SEM 866.0 -t 63.6 unitshl versus 293.0 & 20.5; P < 0.001).Soluble IL-2R levels were highest in patients with generalized disease, were strongly associated with mortality (P < 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL-2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL-2R release. Circulating IL-2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement

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We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.

SUMMARYIn order to assess the direet effects of eyclosporine A (CsA) and rapamycin on B cells, we utilized a two-segment eulture system of highly purified B lymphocytes consisting of induction (activation) in the presenee of the formalinized Staphylococcus aureus bacteria and IL-2. and diiTerentiation, respectively, in the presence of various combinations of cytokines. Results show that rapamycin strongly inhibited produetion of both IgM and IgG measured at the end of the secondary culture stjpported by IL-2/IL-6. whereas CsA up-regulated the immunoglobulin production. The stimulatory efVeet of CsA was also observed when preaetivated B cells were recultured in absence of any cytokines. These results show that rapamycin and CsA have dearly distinct effects on human B lymphocyte responses in vitro. Rapamyein is a more potent in vitro immunosuppressant of B lytnphocytes than CsA. It is effective at significantly lower concentrations, and it does not stimulate either the proliferation or antibody production by preactivated B cells.