Serum levels of soluble interleukin-2 receptor (sIL-2R) in B-chronic lymphocytic leukemia.

By using an enzyme-linked immunosorbent assay, the levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 20 patients with cell chronic lymphocytic leukemia in different stages of disease and in supernatants obtained from enriched B cell suspensions. In either all serum samples or in one out of three supernatants, elevated levels of sIL-2R were found. This could indicate that the B leukemic cells release sIL-2R which in turn, for its potential capacity of binding circulating IL-2, could contribute to the abnormal immunoregulation which characterizes B-CLL. This finding, which needs further investigation, could have prognostic significance.     

The clinical significance of serum soluble interleukin 2 receptor (sIL-2R) concentration in lung cancer

The activated mononuclear cells can release a soluble form of interleukin 2 receptor (sIL-2R) in the blood. Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation. This molecule acts as an antagonist of IL-2-mediated responses. The present study was carried out to analyze the circulating levels of sIL-2R in lung cancer in relation to the histological type of the tumour, clinical stage, response to therapy, time survival for patients. The study included 62 patients (30 SCLC, 32 NSCLC) and 10 healthy subjects as controls. SIL-2R serum levels were measured with a sandwich enzyme immunoassay using commercial kits (ENDOGEN). The mean serum values of sIL-2R were significantly higher in cancer patients than in controls (p=0.01). There was no significant difference in relation to tumour histological type. Within the NSCLC chemotherapy group, sIL-2R mean levels observed at the end of chemotherapy were higher in the progressing patients than in the responding patients. The metastatic patients had higher levels of sIL-2R than those with locally limited disease. In the case of SCLC classified to extensive disease mean levels of sIL-2R were higher than SCLC classified to limited disease. The mean serum values of sIL-2R were significantly higher in weight loss patients than no weight ones (p=0.03). Within NSCLC group there was a correlation between sIL-2R mean levels and the age of patients (p=0.04). In SCLC group there was a correlation between levels of sIL-2R and time survival for patients (p=0.009).     

Identification of a soluble IL-2 receptor beta-chain from human lymphoid cell line cells

A clone was isolated from the human lymphoid cell line YT that displayed IL-2R beta, and was found to express much higher levels of IL-2R beta than the original cells. Combining cell surface iodination, affinity labeling of the released soluble protein, and fluorescence sandwich-ELISA for both IL-2 and IL-2.(soluble)(s)IL-2R beta reactants revealed the presence of IL-2-binding protein in the culture supernatant as soluble forms of IL-2R beta. By using the fluorescence sandwich-ELISA elevated levels of sIL-2R beta were measured in culture supernatants of human T cell leukemia virus I positive T cell lines. In addition to this constitutive production of sIL-2R beta, normal PBMC could release low levels of IL-2R beta by stimulation with PHA. In contrast, this was not found in certain human T cell leukemia virus I negative T cell, B cell and macrophage lines. Immunoprecipitation of the soluble protein with IL-2R beta-specific mAb characterized it as an apparent 50- to 55-kDa molecule that is distinct from the 45-kDa soluble IL-2R alpha. Moreover, 10 to 15% of the total cell surface molecules were released into culture supernatants. These results suggest that the released IL-2R beta might serve as an immunoregulatory function in IL-2 dependent both normal and abnormal immune responses.     

Correlation of serum tumor necrosis factor-alpha,interleukin-4 and soluble interleukin-2 receptor levels with radiologic and clinical manifestations in active pulmonary tuberculosis

The precise clinical manifestations of tuberculosis are likely to result from a complex interaction between the host and the pathogen. We took serum samples from a group of patients with a variety of clinical and radiological stages of pulmonary tuberculosis in order to characterize tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and soluble interleukin-2 receptor (sIL-2R) response. We further evaluated whether the levels of TNF-alpha, IL-4 and soluble IL-2R are related with each other, and also evaluated the levels of TNF-alpha, IL-4 and sIL-2R after anti-tuberculosis therapy and relation with radiologic scores. Forty-three inpatients with active pulmonary tuberculosis and 19 healthy controls participated in the study. Patients were divided into four categories radiologically on chest X-ray (minimal, moderate-advanced, far-advanced and with miliary infiltration). Concentrations of TNF-alpha (20.9+/-10/15.4+/-8 pg/ml) and sIL-2R (2569+/-842/1444+/-514 pg/ml) were statistically different between patients and controls (p=0.02 and p=0.0001, respectively). Before chemotherapy there was a positive correlation between TNF-alpha and sIL-2R (r=0.34), but there was no correlation between IL-4 and TNF-alpha, and between IL-4 and sIL-2R (r=-0.23 and r=-0.22). The TNF-alpha level was not statistically different in four groups before and after chemotherapy. Results of this study provided some evidence confirming the previously reported role of TNF-alpha, IL-4 and sIL 2R in the control of tuberculosis, but these cytokines were not found related with disease severity.     

Serum soluble IL-2 receptor as a marker of lymphocyte activation in some autoimmune diseases. Effect of immunosuppressive therapy

Our experience regarding serum soluble interleukin-2 receptor (sIL-2R) measurement as a marker of lymphocyte activation consists of patients with autoimmune disease: 37 with systemic lupus erythematosus (SLE), 23 with autoimmune hepatitis (AIH), 74 with inflammatory bowel disease and six with Wegener's granulomatosis (WG). The influence of immunosuppressive therapy has also been assessed. Serum sIL-2R in SLE is significantly higher than in healthy controls and good correlation is found between sIL-2R and disease activity. Severity of kidney inflammation in lupus nephritis can be reflected by the increased excretion of sIL-2R. It was found that sIL-2R level significantly falls when the disease becomes clinically inactive after immunosuppressive therapy, but in many cases (up to 50%) it does not reach normal levels. The last finding suggests that lymphocyte activation may still be present even though the disease is considered inactive under clinical criteria and support the need of prolonged immunosuppression after the first signs of remission. In AIH the serum levels of sIL-2R are elevated in all patients with active disease; all cases with "highly active" disease have significantly higher concentrations than patients with "mild activity". A good correlation has been demonstrated between elevated serum sIL-2R values and anti-asialoglycoprotein receptor (ASGPR) titer (the specific marker of AIH). The follow-up study showed a significant decrease of both sIL-2R levels and anti-ASGPR titer after 3-9 month immunosuppressive therapy. The findings support that sIL-2R and anti-ASGPR titer could serve as reliable humoral markers for disease-specific activity. Compared with inactive ulcerative colitis (UC) and Crohn's disease (CD), significantly higher levels of sIL-2R were present in the serum of patients with active disease, and in inactive disease than in healthy age-matched controls. Methotrexate (MTX) therapy of patients with refractory UC resulted in sIL-2R decrease at the end of therapeutic period (20 i.m. injections of once a week 25 mg), good responders showing > 50% decrease even at 5-7 weeks of treatment. Serum sIL-2R is elevated in all six patients with WG. Contrary to anti-neutrophil cytoplasmic antibodies (ANCA), sIL-2R remains elevated above cut-off for normal range, despite clinical improvement following immunosuppressive treatment. The last observation suggests that serum sIL-2R is not a good measure of the disease activity and argue for the need of longer immunosuppressive therapy just after the first days of clinical remission.     

Elevation of soluble interleukin-2 receptor levels in nasal allergy

To investigate soluble IL-2 receptor (sIL-2R) levels in nasal allergy, the sera and nasal secretions from patients with nasal allergy and from healthy subjects were subjected to a double-epitope enzyme-linked immunosorbent assay. Significant elevation of sIL-2R concentrations in the sera and nasal secretions was observed in the allergy patients (n = 26) compared with those of healthy subjects (n = 9). IL-2R-positive (CD25(+)) cells were observed in the crust formed in an allergic nasal mucosa. The concentration of sIL-2R in the sera correlated neither with the eosinophil count of the peripheral blood count nor with clinical severity. The concentration of sIL-2R in the nasal secretions was significantly higher compared with that in the sera from allergic patients (p < 0.01), whereas no significant difference was observed between sIL-2R levels in the sera and nasal sections from normal subjects. These findings indicate that sIL-2R plays an essential role in allergic processes by regulating IL-2R-positive cells recruited into the nasal mucosa.     

Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV

Serum levels of soluble IL-2R (sIL-2R) were measured in blood donors seropositive for HIV. Approximately one-half (53/101) of these seropositive donors exhibited increased serum sIL-2R levels compared with seronegative controls (n = 65). Further, a significant inverse correlation was observed between serum sIL-2R levels and CD4 cell levels in seropositive study participants. These findings suggest that increased serum sIL-2R levels in HIV infection may be linked to CD4 cell loss, and thus reflective of the stage of HIV-induced disease.     

Dynamic changes in soluble interleukin-2 receptor levels during treatment of Graves' disease. Correlation with disease activity

The activation of T lymphocyte is accompanied by the release of soluble interleukin-2 receptors (sIL-2R) which can be assessed in biological fluids. A prospective study of the dynamic changes in sIL-2R levels was performed in the serum of 10 patients undergoing a medical treatment for Graves' disease. All patients received carbimazole during the study and, when necessary, L-thyroxine to compensate hypothyroidism. sIL-2R levels were measured before (M0) and after the 1st (M1), 3rd (M3) and 6th month (M6) of treatment. The levels of sIL-2R were high at M0 and M1, and decreased significantly between M1 and M3 (p = 0.03). At M0, the levels of sIL-2R were highly correlated with triiodothyronine (T3) levels (p = 0.0003), early [131I] uptake (p = 0.007) and, to a lesser degree, with anti-thyrotropin receptor antibody levels (p = 0.02). At M6, no correlation was found anymore. We conclude that sIL-2R levels are increased in patients with untreated Graves' disease. They are highly correlated with the markers of Graves' disease activity and decrease during medical treatment.     

Soluble interleukin-2 receptor in stage I-III melanoma

The aim of the present study was to assess the prognostic value of soluble interleukin-2 receptor (sIL-2R) serum levels in stage I-III melanoma patients. The levels of sIL-2R were determined using an enzyme immunometric test kit in 329 patients affected by malignant melanoma (MM) from 1995 to 2004. Correlations between sIL-2R values, baseline patients and tumour features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to plot disease-free survival (DFS) curves. Univariate analysis was performed with the Log-rank test. Cox proportional-hazards regression was used to analyse the effect of several risk factors on DFS. In total, 2330 blood samples were collected during follow-up of 329 MM patients. Forty-five (13.7%) patients had Breslow tumour thickness1.00 and 2.00 and 4.00 mm. Ulceration was present in 64 cases (19.4%). Thirty-nine sentinel lymph nodes (SLNs) (11.8%) were infiltrated by MM. Soluble IL-2R values ranged from 130 to 1420 U/ml; median value was 500 U/ml. One hundred twenty-one (36.8%) patients presented with sIL-2R>600 U/ml at first measure (FM), 194 patients (58.9%) with values increasing up to or more than 600 U/ml [increasing values (IV) pattern]. A correlation was found between Breslow's tumour values and the IV sIL-2R pattern group (P=0.0304 with chi2 test). Gender, presence of ulceration, Breslow tumour thickness, FM and IV sIL-2R pattern groups had a significant prognostic value for DFS. At multivariate analysis, presence of ulceration, gender, FM and IV sIL-2R pattern groups emerged as independent prognostic factors for DFS. The 5-year DFS rate was 88% for patients with FM<600 U/ml and 76.9% for patients with FM>600 U/ml. In IV pattern, the 5-year DFS rate was 69.5% compared to 87% for patients with no sIL-2R values>600 U/ml during follow-up. sIL-2R values are associated with progression of MM. Further studies are needed to address the role of the IL-2/IL-2R/sIL-2R axis in melanoma biology.     

Tumour necrosis factor-alpha,interleukin-2 soluble receptor and different inflammatory parameters in patients with rheumatoid arthritis

BACKGROUND AND AIMS: Although the participation of cytokines in the pathogenesis of rheumatoid arthritis (RA) seems to be unequivocal, their relationship with current serum markers of this disease is not clear. The present study analyses whether there is any correlation between the levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 soluble receptor (sIL-2R) and the concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and beta(2)-microglobulin in a group of 21 patients with RA, all rheumatoid factor positive. METHODS: The levels of TNF-alpha and sIL-2R were analysed in association with other parameters of inflammation (ESR, CRP and beta(2)-microglobulin). RESULTS: In comparison with the control group, RA patients presented high median levels of both cytokines, TNF-alpha (6.4 pg/ml) and sIL-2R (56 pmol/L), as well as of ESR (34 mm/h), CRP (0.9 mg/dl) and beta(2)-microglobulin (1.6 mg/dl) (p < 0.01). However, only ESR levels in the RA group significantly differ from the control group (p < 0.01). No correlation was found between the inflammatory parameters. CONCLUSIONS: These results suggested that TNF-alpha and slL-2R levels are up-regulated in RA patients but did not significantly differ from the control group. Due to the chronic course of this disease, other inflammatory markers must be identified in order to provide early therapeutic strategies to these patients.     

Serum evaluation of the balance between soluble interleukin-2 and interleukin-4 receptors

To elucidate the usefulness of the simultaneous analysis of the multiple kinds of soluble cytokine receptors, we determined both the soluble interleukin 2 receptor (sIL-2R, Th1-type cytokine receptor) and the soluble interleukin 4 receptor (sIL-4R, Th2-type cytokine receptor) levels in the sera of healthy subjects as reference values and preliminarily applied to evaluate the patients with diarrhea positive (D+) hemolytic uremic syndrome (HUS) as the diagnostic parameter of the severity. Both sIL-2R and sIL-4R levels in the sera of healthy children were significantly higher than those of healthy adults (p<0.01). The serum sIL-2R level of the patients with severe HUS (n=4) was higher than that of the patients with mild/moderate HUS (n=6) at the initial stage (p<0.01) or healthy children (n=51, p<0.01). Whereas, the serum sIL-4R level of both the severe and mild/moderate groups was lower than that of the healthy control children, although there was no significant difference among the three groups. Namely, the soluble receptor balance (sIL-2R/sIL-4R) in the patients with severe HUS may shift. We considered that the evaluation of the balance between soluble cytokine receptors might be informative for the evaluation of the immune states, as well as the conventional cytokine balance (Th1/Th2).     

Serum levels of TNF-alpha,sIL-2R,IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease

AIM: Behçet''s disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. RESULTS: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.     

Clinical Significance of sIL-2R Levels in B-Cell Lymphomas

Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.     

Changes in cytokine production of breast cancer patients treated with interferons

A clinical randomized study was performed on advanced breast cancer patients who were treated by interferons (IFN) beta and gamma in combination with hormonotherapy (Megace or Tamoxifen). Cytokine levels (IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma) and sIL-2R of individual patients before, during (3 months) and after (6 months) therapy were evaluated and correlated to clinical response according to UICC criteria (responder patients-partial or Complete Response versus non-responder patients-Stable/Progression). Decreases in IL-1beta, IL-6 and sIL-2R were associated with clinical response to therapy versus increases in their levels which corresponded to progression of disease. A significant and dramatic increase in IFN-gamma levels was associated with a favourable response to therapy in the IFNs-treated patients, mainly in the group of Tamoxifen. Baseline levels of sIL-2R and of IFN-gamma were prognostic of clinical response and were found to be the most sensitive cytokine parameters for defining the clinical utility of the combination of IFNs and hormonotherapy in breast cancer patients.     

Interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors in patients with solid tumors are not correlated

Activated lymphocytes can release a soluble form of IL-2 receptor (sIL-2R), which retains the capacity to bind IL-2. Abnormally high values of sIL-2R have been observed in patients with advanced solid tumors. In an attempt to further understand the biological significance of sIL-2R in solid tumors, this study investigated the relation between sIL-2R and Tac-positive cells. sIL-2R serum levels and Tac-positive cells were determined in 18 patients with solid tumors metastatic, 108 non-metastatic. Tumor types were: breast 7; lung 6; colon 2; stomach 1; testis 1; larynx 1. No correlation was found between circulating sIL-2R values and Tac-positive cells, and there was no difference between Tac-positive cell mean number in patients with high and normal sIL-2R levels. These preliminary results suggest that different mechanisms are responsible for sIL-2R release in the blood and IL-2 receptor expression on the immune cell surface.     

Serum IL-1beta,sIL-2R,IL-6, IL-8 and TNF-alpha in schizophrenic patients,relation with symptomatology and responsiveness to risperidone treatment.

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia     

Lack of changes in soluble interleukin-2 receptor serum levels during chemotherapy-induced lymphocyte damage

The biological significance of soluble IL-2 receptors (sIL-2R) is still unknown; in particular, it is not yet clear whether their increase in the blood may reflect activation of immune cells, or whether it is related to an immune dysfunction. To investigate this problem, we evaluated serum levels of sIL-2R before and after administration of a highly lymphocytolitic chemotherapy (FEC: fluorouracil, epirubicin, cyclophosphamide) in a group of 6 patients with advanced breast cancer. SIL-2R were analyzed in relation to lymphocyte number. Absolute mean number of lymphocytes was significantly lower after than before chemotherapy. On the contrary, no significant difference was seen in sIL-2R mean levels, and no significant correlation was observed between changes in sIL-2R and in lymphocyte number following chemotherapy. These results would exclude that sIL-2R may simply be due to a passive release following lymphocytic damage.     

Soluble interleukin-2 receptors in ulcerative colitis

T-Cell activation results in the release or shedding of a soluble form (45 kDa) of the cellular (55 kDa) low-affinity interleukin-2 receptor (alpha-chain) (slL-2R). The present study was performed to investigate if the serum concentration of sIL-2R is a marker of disease activity in patients with ulcerative colitis (UC), a chronic inflammatory bowel disease. Twenty-seven UC patients (about half of them in remission) and 13 healthy volunteers were studied, sIL-2R concentrations were measured by an enzyme-linked immunosorbent assay, and significantly elevated median sIL-2R values were found in clinically active UC (150 pg/ml; range 100-420), compared to inactive UC (145 pg/ml; range 110-255), and healthy controls (110 pg/ml; range 80-165) (p < 0.01). There was no correlation between sIL-2R concentrations and extent of the disease. Due to the overlap of serum sIL-2R concentrations between different disease stages and controls, the general diagnostic value seems to be limited. However, since slL-2R release is an IL-2 dependent phenomenon, we conclude that the demonstration of increased serum sIL-2R concentrations in UC suggests the existence of an enhanced T-cell activation in vivo in this disease. Further longitudinal studies are required to elucidate if repeated measurements of sIL-2R levels provide an additional way of monitoring UC disease activity in individual patients.     

Serum level of soluble interleukin-2 receptor α correlates with the clinical course and activity of Wilms’ tumour and soft tissue sarcomas in children

Wilms’ tumour (WT) and soft tissue sarcomas (SA) in children lack reliable biochemical markers. This study was carried out to determine the clinical significance of serum soluble interleukin-2 receptor α (sIL-2Rα) in the diagnostics and treatment monitoring of children with WT and SA. The study included 48 children: ten with WT, eight with SA and 30 healthy controls. The sIL-2Rα levels (ELISA) and rates of elevated sIL-2Rα values were estimated prospectively at diagnosis and in complete remission during treatment and after therapy. As the dependence on age was determined, the levels of sIL-2Rα were expressed as multiplications of the upper value of the normal range for a particular age (xN). Median pretreatment levels of sIL-2Rα in patients exceeded those of healthy controls (1.79 xN for WT and 1.53 for SA vs. 0.61 for controls; p<0.001) as did the rates of elevated sIL-2Rα values (80% of WT and 87.5% of SA patients vs. 0% of controls). Good response to therapy was paralleled by a significant decline of pretreatment sIL-2Rα levels and its elevated rates. Thus, sIL-2Rα determination may be of some value in the diagnostics and treatment monitoring of childhood WT and SA.     

High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells

Backgorund: Although increased serum levels of soluble interleukin-2 receptor (sIL-2R) and their clinical importance are well known in mature type lymphoproliferative disorders (LD), little data is available about such information in acute type hematological malignancies. Methods: We examined the serum levels of sIL-2R in 57 adult patients with acute type leukemias: 32 with acute myeloid leukemia (AML), 14 acute lymphoblastic leukemia (ALL) and 11 chronic myelocytic leukemia in blast crisis (CMLBC), and in 29 adult patients with mature type LD, and assessed their cellular and clinical relevance in acute type leukemias. Results: No significant differences were seen in the sIL-2R levels between acute type leukemias and mature type LD. In AML, serum sIL-2R levels were related to the cell surface CD4 expression on blast cells, and patients with higher levels ≧2000U/ml had a poorer prognosis (lower response to chemotherapy and shorter overall survival). Conclusions: These results suggest that serum sIL-2R level elevates in acute type leukemias like mature type LD, and increased sIL-2R levels in adult AML are correlated with certain biological and clinical characteristics.