Interleukin-1α, interleukin-2, and soluble interleukin-2 receptors in polymyositis

Cell-mediated immunity has been implicated in the pathogenesis of polymyositis (PM). We conducted a prospective study in which serum levels of soluble interleukin-2 receptors (IL-2R), IL-1α, and IL-2 were correlated with creatine kinase (CK) levels and clinical disease activity. Cytokines and IL-2R were quantitated in 133 serum samples from 14 patients by use of an enzyme-linked immunosorbent assay. In patients with acute PM (9 patients), soluble IL-2R and IL-1α levels were elevated initially, but declined rapidly with therapy. A significant linear relationship was found between soluble IL-2R levels and CK levels. IL-2 was initially detectable in only 3 patients, and it disappeared with therapy in all 3. The levels of cytokines and IL-2R were consistently normal in patients with inactive PM (2 patients). In patients with chronic PM (3 patients), the cytokines and soluble IL-2R levels were normal despite persistently abnormal CK levels and/or muscle weakness. Cellular IL-2R levels correlated positively with serum levels of soluble IL-2R. Our studies substantiate a pathogenic role for cellular immunity in PM, with the finding of activation of lymphocytes. The finding of increased levels of IL-1α demonstrates for the first time that there is monocyte activation in PM. Persistent elevation of CK levels after normalization of the levels of cytokines and IL-2R may be prognostic of impending chronic disease. Serum soluble IL-2R appear to be a sensitive indicator of improvement or exacerbation of disease activity in patients with PM.     

Serum levels of IL-2, IL-1 alpha, TNF-alpha, and soluble receptor of IL-2 in HIV-1-infected patients.

Serum levels of the interleukins (IL-1 alpha, IL-2), tumor necrosis factor-alpha (TNF-alpha), and soluble receptor of IL-2 (sIL-2R) were studied by enzyme-linked immunosorbent assay (ELISA) in 12 normal healthy controls and 52 HIV-1 seropositive patients. Results indicated that: (1) sIL-2R levels were significantly increased in most HIV-1 seropositive patients. This increase appeared to be correlated with low CD4 cell counts and with the presence of detectable levels of p25 antigen. Furthermore, initially high levels of sIL-2R appeared to be correlated with progression of disease. (2) IL-2 levels were found to be increased in about 43% of asymptomatic carriers (ASY) and subjects with lymphoadenopathy-associated syndrome (LAS) compared with 12% in the case of AIDS-related complex (ARC) and AIDS patients. (3) There was a positive correlation between serum levels of TNF-alpha and IL-1 alpha in nearly all patients. Detectable levels of both cytokines were found in 34% of ASY and LAS patients and only rarely were detectable in ARC and AIDS patients. (4) Sixteen patients in whom progression of disease was observed were studied initially and at the moment they upstaged. No significant modification of serum levels of the three cytokines and sIL-2R studied could be evidenced. It was concluded that sIL-2R could be a useful marker of disease activity and progression, though a prospective study is necessary. For IL-2, IL-1 alpha, and TNF-alpha, this study indicated the presence of variable alterations in serum levels in HIV-1-infected patients.     

Serum levels of interleukin-10, interleukin-12 and soluble interleukin-2 receptor in chronic liver disease type C

BACKGROUND/AIMS: It is still unclear whether and how Th1/Th2 type cytokines are involved in the progression of chronic liver disease type C. We therefore examined serum levels of IL-10, IL-12 and sIL-2R (soluble IL-2 receptor) in association with clinical parameters in chronic liver disease type C, whereas IL-12 and sIL-2R represent Th1 cytokine and IL-10 does Th2 cytokine, respectively. METHODOLOGY: Serum levels of IL-10, IL-12 and sIL-2R were measured in 110 patients, including 36 with chronic hepatitis, 24 with liver cirrhosis and 50 with hepatocellular carcinoma in comparison with 19 normal individuals, by an enzyme-linked immunosorbent assay. In 9 chronic hepatitis patients, serum levels of these cytokines were measured before and after interferon therapy. In 28 with hepatocellular carcinoma, they were also measured before and after transcatheter arterial embolization. RESULTS: Serum levels of IL-10 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 3.9 +/- 1.8 pg/mL, 5.7 +/- 6.4 pg/mL and 5.6 +/- 8.9 pg/mL, respectively. IL-10 level was significantly correlated with level of y-globulin. Serum levels of IL-12 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 347.4 +/- 150.3 pg/mL, 365.2 +/- 130.7 pg/mL and 399.4 +/- 258.2 pg/mL. sIL-2R levels in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma were 614.6 +/- 223.5 U/mL, 878.7 +/- 330.5 U/mL and 1037.9 +/- 412.0 U/mL. Serum levels of IL-12 and sIL-2R were significantly elevated on day 7 after interferon therapy compared to day 0 (p < 0.05 and p < 0.001, respectively), while no significant difference was seen in IL-10. Serum level of IL-10 was significantly elevated on day 3, and that of sIL-2R was elevated on day 3 and 7 after transcatheter arterial embolization, while that of IL-12 was decreased on day 3 and 7. CONCLUSIONS: The results of the present study suggest that Th1/Th2 type cytokines are changed in association with progression of chronic liver disease type C and in response to therapy.     

Frequently relapsing Crohn's disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission

We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up starting from a remission period were studied retrospectively. Relapses were defined by a retrospective calculation of the Crohn's disease activity index or by the clinical judgement of the physicians in charge of the patients. Disease course over the study period was assessed by the mean number of annual relapses. Analysis used measurements during remission of the following: erythrocytes sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin-6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the study period 21 patients experienced at least one relapse and 15 did not. Mean serum levels of sIL-2R and mean relative lymphocytosis in remission significantly discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1 (sensitivity of 76% and specificity of 80%). The only features correlated with mean number of annual relapses in the relapsing patients were mean serum levels of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate analysis demonstrated statistical significance only for the mean serum level of IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum levels during remission corresponds to chronic active disease, while high serum levels of IL-6 in these patients is associated with a high frequency of relapse.     

Soluble interleukin-2 receptors in systemic lupus erythematosus

We studied levels of soluble interleukin-2 receptors (IL-2R), which are released by activated lymphocytes, in 139 serum samples from 12 patients with systemic lupus erythematosus (SLE). Concentrations of soluble IL-2R were significantly increased in SLE patients compared with controls (P less than 0.001), and they were significantly higher in patients during active SLE defined by low C3 levels (P less than 0.001), low C4 levels (P less than 0.001), or proteinuria (P less than 0.05) than during inactive SLE. Elevated levels of soluble IL-2R correlated with hypocomplementemia in longitudinal studies (P less than 0.001). Measurement of serum concentrations of soluble IL-2R may provide a sensitive and specific method for monitoring disease activity and immune activation in patients with SLE.     

Elevation of soluble interleukin-2 receptor in patients with non-small cell lung cancer treated with gefitinib

Purpose We previously reported that plasma thromboxan B₂, soluble P-selectin, and serum regulated on activation, normal T-cell expressed and secreted (RANTES) were elevated after gefitinib treatment. We hypothesized that gefitinib could activate T-lymphocytes via activated platelets, and so we measured serum levels of soluble interleukin-2 receptor (sIL-2R) in patients medicated with gefitinib. Methods Twenty-one patients with non-small cell lung cancer (NSCLC) were entered into this study. All patients received gefitinib over 2 weeks without severe adverse effects. Blood samples were withdrawn from all patients before and after the administration of gefitinib and plasma soluble P-selectin, serum RANTES, and serum sIL-2R were measured by enzyme-linked immunosolvent assay. In addition, we carried out the basic study of the interleukin-2 receptor (IL-2R) expression on CD4⁺ lymphocytes by RANTES.Results Plasma soluble P-selectin, serum RANTES, and serum sIL-2R levels increased significantly in patients receiving gefitinib treatment for 1 and 2 weeks. RANTES did not induce the expression of IL-2R on CD4⁺ lymphocyte. However, the anti-CD3 monoclonal antibody-induced expression of IL-2R was enhanced by the addition of RANTES.Conclusion Our finding indicated that lymphocytes were activated by gefitinib treatment. We think that sIL-2R elevation after gefitinib administration may be a factor positively effecting patients with NSCLC. It is deemed possible that the effect of gefitinib is induced not only by its blocking of the tyrosine kinase of epidermal growth factor receptor but also by antitumor immunity via its activation of T-cells.     

Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid patients: correlations with disease activity

The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive marker of lymphocyte activation, has been proposed as an indicator of disease activity and outcome in patients with inflammatory diseases characterized by the activation of immune cells. Serum sIL-2R levels have been reported higher in rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with RA and in the synovial fluid of 25 of these patients and we compared it with levels found in the serum of 13 healthy controls. Serum sIL-2R levels were significantly elevated in RA patients compared with the healthy agematched control group (P<0.005). The mean level of soluble IL-2R in synovial fluids was significantly higher than the mean sera levels in RA patients (P<0.0001). Moreover, we examined the correlation between serum and synovial fluid sIL-2R levels and disease activity measures. Serum sIL-2R correlated only with ESR (P<0.04). The synovial fluid sIL-2R correlated with ESR (P<0.02) and a visual analogue scale (VAS) pain score (P<0.04). Both serum and synovial fluid sIL-2R levels correlated with the chronic arthritis systemic index (CASI; P<0.04 and P<0.005, respectively). Our data suggested that in RA the measurement of sIL-2R may certainly mirror the degree of chronic inflammation and the continuous activation of the immune cells in the joint, although the role of this molecule in the immune response is still unclear.     

Elevated concentrations of soluble interleukin-2 receptors in serum samples and bronchoalveolar lavage fluids in active sarcoidosis

Sarcoidosis is a granulomatous disorder of unknown cause characterized by activation of T-lymphocytes. We here report the use of an enzyme-linked immunosorbent assay for the soluble interleukin-2 receptor (IL-2R) as a measure of T-cell activation in serum samples and bronchoalveolar lavage fluids in 15 patients with active sarcoidosis. The geometric mean (x divided by SEM) value for soluble IL-2R in serum samples from patients with sarcoidosis was 1,110 (x divided by 1.17) versus 224 (x divided by 1.08) U/ml for normal control subjects (p less than 0.001). Detectable levels of soluble IL-2R were present in bronchoalveolar lavage fluids from 10 of 15 patients with sarcoidosis versus only 2 of 36 normal control subjects (p less than 0.001). Levels of soluble IL-2R in serum samples from untreated patients with sarcoidosis correlated with 67gallium lung scanning scores (p less than 0.05) but not with serum angiotensin-converting enzyme concentrations or constituents of bronchoalveolar lavage. In 5 patients, the level of soluble IL-2R in serum samples fell from 1,499 (x divided by 1.20) to 476 (x divided by 1.58) U/ml (p less than 0.05) after 6 wk of successful treatment with corticosteroids, whereas the changes in soluble IL-2R in bronchoalveolar lavage fluids were more variable. These observations suggest that measurements of soluble IL-2R, particularly in serum samples, may reflect disease activity and be clinically useful in the management of patients with sarcoidosis.     

Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia.

Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty-seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated.     

Elevated soluble interleukin-2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis

In a previous study, we used an enzyme-linked immunosorbent assay to measure soluble human interleukin-2 receptors (IL-2R), and found that when activated lymphocytes produce cell-associated IL-2R, they also release a soluble form of IL-2R into culture supernatants in vitro. Soluble IL-2R have also been detected circulating in vivo at low levels in the serum of healthy individuals, and at abnormal levels in a variety of diseases, particularly those where immune dysfunction is thought to play an important role. We therefore evaluated serum IL-2R levels in 77 patients with rheumatoid arthritis (RA), and compared them with levels in 46 age-matched healthy controls. Nineteen additional RA patients with concurrently obtained sera and synovial fluid (SF) samples were compared with 14 patients with osteoarthritis of the knee or hip. The serum IL-2R levels were significantly elevated in RA patients, compared with the control groups (P less than 0.0001). Serum IL-2R levels in the RA patients did not correlate with disease activity as determined by a variety of clinical and laboratory parameters. RA SF IL-2R levels were significantly higher than corresponding RA serum IL-2R levels (P = 0.0001). No such difference was noted in the osteoarthritis group, where serum and SF IL-2R levels were comparable with serum levels in healthy controls. These findings support the hypothesis that in vivo lymphocyte activation plays an important role in RA; moreover, soluble IL-2R measurement in serum and SF may be a very useful way to identify patients at risk for, or manifesting, a chronic immune-mediated inflammatory arthropathy.     

Soluble interleukin-2 receptor levels in patients with pulmonary tuberculosis

Utilizing an enzyme-linked immunosorbent assay, we detected markedly elevated serum levels of soluble interleukin-2 (IL-2) receptors in patients with untreated pulmonary tuberculosis. In these patients, we also found that serum levels of soluble IL-2 receptors were closely correlated with serum adenosine deaminase levels (r = 0.869, p less than 0.001). Therefore, serum soluble IL-2 receptors appear to reflect the existence of active cell-mediated immunity in pulmonary tuberculosis and may prove to be a useful immunological marker for pulmonary tuberculosis.     

The oxygen stress index and levels of circulating interleukin-10 and interleukin-6 in patients with chronic heart failure

OBJECTIVES: We sought to study circulating levels of pro- and anti-inflammatory cytokines together with the oxygen stress index in patients with chronic heart failure (CHF). BACKGROUND: Patients with CHF exhibit elevated levels of inflammatory and anti-inflammatory cytokines but the relative level of these cytokines with the oxygen stress index have not been reported. METHODS: Twenty-two patients with CHF and 10 control subjects were studied. Plasma levels of IL-6 and IL-10 were determined and the oxygen stress index was evaluated by urine 8-iso-PGF2alpha estimations. RESULTS: Plasma levels of IL-6 and IL-10 in CHF patients were significantly higher than those observed in the control subjects. Patients with more advanced disease (higher NYHA class) showed higher concentrations of IL-10 and IL-6 than those with less serious disease. 8-iso-PGF2alpha urine concentration (and therefore the oxygen stress index) was significantly higher in patients with CHF in comparison with control subjects. IL-6 plasma levels, but not IL-10 concentrations, correlated significantly with 8-iso-PGF2alpha levels in urine. CONCLUSIONS: Inflammatory and anti-inflammatory cytokine levels, as well as the oxidative stress index, are increased in patients with chronic heart failure. Inflammatory cytokine IL-6, but not anti-inflammatory cytokine Il-10, levels correlated significantly with the oxygen stress index.     

Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma.

OBJECTIVE. To determine whether interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-4, interferon-gamma (IFN gamma), IL-6, and tumor necrosis factor alpha (TNF alpha) are detected more frequently in sera from scleroderma patients than in sera from controls. METHODS. Serum concentrations of these cytokines were measured in 78 scleroderma patients and 73 controls, using enzyme-linked immunosorbent assay, radioimmunoassay, and bioassay techniques. RESULTS. IL-2, IL-4, and IL-6 were each detected more frequently in sera from scleroderma patients than in sera from controls. TNF alpha and IL-1 alpha were found with equal frequency in patient and control sera. IL-1 beta and IFN gamma were not detected in any sera. CONCLUSION. IL-2, IL-4, and IL-6 may be among the cytokines that contribute to the disease process in scleroderma patients. To our knowledge, this is the first report of elevated serum IL-4 levels in human disease.     

Increased levels of serum interleukin-18 in Graves' disease.

We have previously reported that serum soluble interleukin-2 receptor (sIL-2R) and IL-12 levels were significantly increased in hyperthyroid Graves' disease. In this study, we investigated serum IL-18 levels in patients with either Graves' disease or Hashimoto's thyroiditis. The serum IL-18 levels in Graves' disease were significantly increased in the hyperthyroid state and were decreased during treatment with methimazole or propylthiouracil. On the other hand, the levels in Hashimoto's thyroiditis in the hypothyroid state showed no significant differences from those in healthy subjects. When liothyronine sodium was administered orally to healthy subjects, serum IL-18 levels were not changed. Positive correlations between serum IL-18 and IL-12, IL-12 and sIL-2R, and sIL-2R and IL-18 levels were noted in Graves' disease. These results suggest that Th1 cytokines might play an important regulatory role in Graves' disease.     

Interleukin-6, soluble interleukin-2 receptor and soluble interleukin-6 receptor in the sera of patients with different histological patterns of rheumatoid synovitis

OBJECTIVE: The present study was conducted to investigate whether the serum levels of interleukin 6 (IL-6), soluble IL-2 receptor (sIL-2R) and sIL-6R are associated with the morphological appearance of rheumatoid arthritis (RA). METHODS: Using the ELISA technique we measured the IL-6, sIL-2R and sIL-6R concentrations in the serum of 34 patients with RA and 28 patients with osteoarthritis (OA). Histological analysis of synovial samples distinguished 2 types of rheumatoid synovitis. Twenty-one RA specimens presented diffuse infiltrates of mononuclear cells without any specific microanatomical organization. In remaining 13 samples the formation of lymphocytic follicles with germinal center-like structures was found. RESULTS: Serum levels of IL-6, sIL-2R and sIL-6R were elevated in patients with RA compared to the OA control group (p < 0.001, p < 0.001 and p < 0.05 respectively). Concentrations of IL-6 and sIL-2R were highest in the serum of RA patients with follicular synovitis in comparison to patients with diffuse synovitis (p < 0.001 and p < 0.01 respectively) and could distinguish RA patients with these two histological variants of the disease. Serum levels of IL-6 and sIL-2R correlated with markers of disease activity such as ESR and CRP levels. In addition, the clinical data suggest a more severe disease among RA patients with follicular synovitis. CONCLUSION: Distinct histological types of rheumatoid synovitis associated with unique serum concentrations of IL-6 and sIL-2R reflect levels of disease activity and confirm the concept of RA heterogeneity.     

Elevated serum levels of soluble interleukin 2 receptor, interleukin 2 and neopterin in diffuse and limited scleroderma: effects of chlorambucil

In a study of 48 patients with systemic sclerosis (SSc). elevated serum levels of soluble interleukin 2 receptor (IL-2R), interleukin 2 (IL-2) and neopterin (indicators of lymphocyte/monocyte activation) were noted in 100, 44 and 40% of early untreated patients with SSc (11 diffuse, 5 Limited). Levels of IL-2R, but not IL-2 or neopterin, were lower in patients with longer duration of disease and possibly with chlorambucil therapy. Pharmacologic alterations of markers of humoral or cell mediated immunity may not be an accurate reflection of clinical efficacy of chlorambucil.     

Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.     

Plasma interleukin-2 and a soluble/shed interleukin-2 receptor in serum of patients with Crohn's disease. Effect of cyclosporin.

Circulating concentrations of interleukin-2 (IL-2) and a soluble or shed form of the IL-2 receptor (sIL-2R) were determined by enzyme-linked immunosorbent assays (ELISA) in 61 patients with chronic active Crohn's disease (CD) initially and during a three month placebo controlled trial of cyclosporin 5-7.5 mg/kg/day. The baseline median (25-75% range) plasma IL-2 concentration was 0.6 ng/ml (0.3-2.85 ng/ml) in patients who did not receive prednisolone, 0.5 ng/ml (0.23-3.4 ng/ml) in patients who did (not significant), and 0 ng/ml (0-0.07 ng/ml) in control subjects (p less than 0.00001). The corresponding median serum sIL-2R concentrations were 747 U/ml (580-1287 U/ml), 540 U/ml (422-616 U/ml) respectively in CD patients (p = 0.006) and 320 U/ml (268-406 U/ml) in control subjects (p less than 0.00001). Increased concentrations of plasma IL-2 and serum sIL-2R were seen in 66% and 81% of the patients, respectively. A fall in serum sIL-2R was only seen in patients who improved with cyclosporin treatment (p = 0.006). At month 3 the median serum sIL-2R concentration was 440 U/ml (400-668 U/ml) v 801 U/ml (534-1067 U/ml) in patients not responding to cyclosporin (p = 0.003). No changes occurred in the placebo group. These results suggest that the IL-2 dependent pathway of immune activation is upregulated in vivo in CD and that cyclosporin may interfere with this process.     

Soluble interleukin 2 receptors in patients with sarcoidosis. Possible origin.

We determined levels of soluble interleukin 2 receptors (IL-2R) in patients with sarcoidosis and further examined their origin. Thirty-nine patients with sarcoidosis and 18 healthy control subjects were studied. Soluble IL-2R levels in serum were significantly higher (p < 0.01) in sarcoidosis than in control subjects. In sarcoidosis, levels of soluble IL-2R in serum were significantly higher (p < 0.05) in patients with active disease than those with inactive disease and were significantly (p < 0.01) correlated with serum angiotensin-converting enzyme (ACE) levels. IL-2R expression on monocytes and alveolar macrophages (AMs) was significantly (p < 0.01) increased in patients with sarcoidosis as compared with control subjects. Soluble IL-2R levels in the supernatants of cultured monocytes and AMs were higher in patients with sarcoidosis than in control subjects. Those of cultured T lymphocytes obtained from peripheral blood and bronchoalveolar lavage fluid were detected in some patients with sarcoidosis, while undetected in control subjects. Furthermore, soluble IL-2R in serum was significantly correlated with soluble IL-2R in the supernatants of cultured monocytes and AMs (p < 0.01 and p < 0.05, respectively). These results demonstrate that soluble IL-2R in serum is a useful index of the disease activity of sarcoidosis and is mainly derived from monocytes and AMs.     

The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors

Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin- 2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is "activated" in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.