Serum Soluble Interleukin-2 Receptor Research Articles

Serum levels of IL-6 and its soluble receptor (sIL-6R) in Waldenström's macroglobulinemia.

Interleukin-6 (IL-6) is a multifunctional cytokine that plays roles in the immune response, inflammation and hematopoiesis. Serum IL-6 levels have reported to reflect disease severity and high tumor burden in multiple myeloma (MM) patients and to correlate with several other laboratory parameters. Serum-soluble IL-6 receptor (sIL-6R) plays an agonist role in IL-6 signaling, enhancing its biological activity tenfold. PURPOSE-METHODS: We measured IL-6 and sIL-6R levels in 11 patients (7 male, 4 female, mean age 66.9 yr) with Waldenström's macrobulinemia (WM) using a commercially available enzyme-linked immunoassay in order to investigate their biological role and to find any possible relationship with disease severity, tumor burden or response to treatment. Serum IL-6 and sIL-6R concentrations at diagnosis were significantly higher than in healthy controls (Mann Whitney U-test, p < 0.001 and p < 0.01, respectively). Patients who were effectively treated had a significant reduction in IL-6 levels (p = 0.017). With regard to sIL-6R levels, no specific tendency was observed. In some of the responsive patients the levels increased whereas in others they decreased. No correlation was found between IL-6 and sIL-6R levels at diagnosis (p = 0.9, r = 0.036) or after treatment (p = 0.083, r = 0.3). Our results suggest that IL-6 may be a marker reflecting tumor burden, disease severity and response to treatment in WM. With regard to sIL-6R, we believe that it does not seem to be of much value, and its role remains to be clarified. However, future studies are needed to confirm and further extend the present results.

Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma.

Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma. © 2000 Cancer Research Campaign

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.

The clinicopathologic significance of preoperative serum-soluble interleukin-2 receptor concentrations in operable non-small cell lung cancer patients

Background Serum-soluble interleukin-2 receptor (IL-2R) concentrations have been found to be elevated in cancer patients. However, the importance of this finding in patients with non-small-cell lung cancer (NSCLC) has not been previously established.

Impaired interleukin‐2 response of mononuclear cells in Guillain–Barré syndrome

We studied the production of and response to interleukin-2 (IL-2) by cultured peripheral blood mononuclear cells (PBMC) and the soluble IL-2 receptor levels in 10 patients with GBS (eight men and two women) aged 23-67 years. The first blood sample was obtained within seven days of the onset of neuropathic symptoms, and blood samples were collected serially after treatment with plasma exchange. PBMC from GBS patients were found to produce little IL-2 and to have a low response to IL-2 soon after the onset, but marked improvement was seen within one month, concomitantly with improvement of neuropathic symptoms. Serum soluble IL-2 receptor levels were increased at the onset, but gradually decreased thereafter. Our findings suggest that primary immune response in acute-stage GBS may be downregulated via a decrease in the function of PBMC that had previously been activated by interacting with the antigen.

The clinicopathological significance of preoperative serum-soluble interleukin-2 receptor concentrations in operable non-small-cell lung cancer patients.

Serum-soluble interleukin-2 receptor (IL-2R) concentrations have been found to be elevated in cancer patients. However, the importance of this finding in patients with non-small-cell lung cancer (NSCLC) has not been previously established. Preoperative serum-soluble IL-2R concentrations were determined in 65 consecutive patients with operable NSCLC. The correlation of preoperative serum-soluble IL-2R concentrations with various clinicopathological features of this cancer was evaluated to clarify the clinical significance of this parameter. Although serum-soluble IL-2R concentrations were not significantly higher in operable NSCLC patients than in normal controls (P = .1180), serum-soluble IL-2R concentrations were significantly higher in patients with stage IIIB or IV disease than in normal controls (P = .0001). The presence of intrapulmonary metastasis was the only clinicopathological feature that was significantly correlated to serum-soluble IL-2R concentration (P = .0004). The sensitivity of serum-soluble IL-2R concentration in identifying the presence of intrapulmonary metastasis was 87.5%; specificity was 75%. Elevated preoperative serum-soluble IL-2R concentrations in patients with operable NSCLC reflect the occurrence of intrapulmonary metastasis. Preoperative examination of serum-soluble IL-2R concentrations may be valuable in the detection of the intrapulmonary metastasis preoperatively.

Increased serum-soluble interleukin-2 receptor in burn patients: characterization and effects on the immune system

The consequences of high serum concentrations of the interleukin (IL)-2 receptor α chain (sIL-2Rα) in several diseases are poorly understood. The objective of this study was to determine the form of sIL-2Rα in burn patients and its biological role. sIL-2Rα was measured in 18 severely burned individuals who received nutritional support with a normal or low fat content. sIL-2Rα was elevated throughout the study and it was notably lower in patients fed a low fat diet. Serum IL-6 and sIL-2Rα significantly correlated ( r = 0.74, p < 0.05) in burn patients. The presence of sIL-2Rα was associated with a decrease in DR molecules in the CD2 − and CD11b + cells of these patients. Western blot analysis of serum protein with N-terminal or C-terminal specific antibodies indicated that sIL-2Rα represents the extracellular domain of this molecule. Patient serum inhibited specifically murine, but not human IL-2–dependent T-cell proliferation. To determine the significance of sIL-2Rα, recombinant sIL-2Rα was used in different cellular model involving IL-2. sIL-2Rα inhibited natural killer cell activity by 50% in the presence of IL-2. The basal proliferation of peripheral blood mononuclear cells was inhibited by sIL-2Rα, but phytohemagglutinin-induced proliferation was unaffected by this form of receptor. Interferon (INF)-γ production induced by OKT-3 on peripheral blood mononuclear cells was not altered by sIL-2Rα, but IL-2 induced increase in INF-γ production was suppressed. The decreasing production of INF-γ in the presence of IL-4 was significantly increased in the presence of sIL-2Rα in media. These results show that the large amount of sIL2-Rα circulating in burn patients is related to the inflammatory response. The amount of dietary fat modulates sIL2Rα concentration in burn patients, confirming the beneficial effect of low fat administration after burn trauma. Inhibition of T-cell activation in burn patients is not directly related to sIL-2Rα, although the presence of sIL-2Rα in serum can inhibit some IL-2 mediated response, such as the emergence of TH1 and TH2 cells.

Prognostic Significance of Serum Soluble Interleukin-2 Receptor Level in Non-Hodgkin's Lymphoma: A Single Center Study in Japan

Interleukin 2 receptor is expressed not only on the surface of activated T or B lymphocytes, but also on certain lymphoid malignancies. The receptor is released from the cell membrane as soluble form (sIL-2R). Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation or specific tumor cell growth including non-Hodgkin's lymphoma (NHL). However, the relevance of serum sIL-2R levels relating to clinical outcome in adult patients with NHL remains uncertain. Therefore, we investigated the serial serum sIL-2R levels in 28 untreated patients with NHL to evaluate its correlation with clinical characteristics. High serum sIL-2R level (>1000 U/ml) at diagnosis was associated with a high incidence of treatment failure (p=0.03) and poor overall survival (p=0.057). The serum sIL-2R levels decreased significantly after achieving complete remission (p=0.003). Further larger studies are required to evaluate whether serum sIL-2R level is an independent prognostic factor or not. However, adding this parameter to those already employed in the International Prognostic Index would perhaps provide a better prognostic index for adult patients with NHL.

Oestrogens prevent the increase of human serum soluble interleukin-6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro.

Interleukin-6 (IL-6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL-6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL-6 and of soluble IL-6 receptor (sIL-6R) in vivo. Thirty-seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 microg/d) 1 month after surgery (n = 16). Hysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL-6R rose progressively after ovariectomy (mean +/- SEM: 31 +/- 9% and 38 +/- 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1-year period. A similar pattern was also found for serum IL-6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL-6R levels and FSH (r = 0.59; P < 0. 01), oestradiol (r = - 0.43; P < 0.01), testosterone (r = - 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL-6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL-6R in a human osteoblastic cell-line (MG-63) and in a tumour-derived osteoclastic cell line (GCT-51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL-6R and the protein kinase-C activator PMA (10-8 M) increased the release of sIL-6R by osteoblasts more than 3-fold. More strikingly, 17beta E2 (but not 17alpha) significantly inhibited both the spontaneous- and PMA-induced release of sIL-6R by osteoblastic cells (P < 0.05). These results indicate that oestrogen loss causes alterations of the IL-6 system, and that sIL-6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.

Immunomodulatory and therapeutic effect of lentinan in treating condyloma acuminatum

Objective: To observe the immunomodulatory and therapeutic effect of lentinan in treating condyloma acuminatum (CA).Methods: Thirty-six CA patients were randomly divided into two groups, 19 in the treated group treated with lentinan and CO2 laser irradiation, and 17 in the control group, treated with laser irradiation alone. Their T lymphocyte subsets of peripheral blood and level of serum interleukin-2 (IL-2) and soluble interleukin-2 receptor (SIL-2R) were determined before and after treatment, and the recurrence rates of the two groups were compared.Results: After treatment, in the treated group, the CD4/CD8 ratio, serum IL-2 raised and serum SIL-2R lowered significantly (P < 0.05, 0.05, 0.05 respectively) as compared with before treatment, while those parameters were not changed significantly in the control group. The recurrence rate of the treated group was lower than that of the control group.P < 0.05.Conclusion: Lentinan could modulate the cellular immunofunction of CA patients and reduce the recurrence rate of CA cases.

Salivary and serum soluble interleukin-2 receptor in primary Sjögren’s syndrome

Salivary and serum concentrations of soluble interleukin-2 receptor (sIL-2R) were studied in a group of patients with Sjögren’s syndrome and a group suffering from dry mouth. Salivary sIL-2R levels was significantly higher (57.9±15.1 vs 16.7±4.7 pg/ml) ( p<0.05) in the group of 26 patients with Sjögren’s syndrome than in the dry-mouth group. Both the salivary and the serum sIL-2R of normal controls were below the level of detection. No significantly statistical differences were noted between the concentrations of serum sIL-2R in either abnormal groups. No correlations were found between salivary or serum sIL-2R and the erythrocyte sedimentation rate, C-reactive protein, the presence of various autoantibodies or the focus score from lip biopsies in the group of patients with Sjögren’s syndrome. The results show that, although the salivary sIL-2R does not actually reflect the extent of inflammation, it might have an important role in the diagnosis of Sjögren’s syndrome.

Soluble Interleukin 2 Receptors' Levels Versus Thyroid Hormones Levels in Nonthyroidal Disease

Serum soluble interleukin-2 receptor levels, basal thyrotropin, total thyroxine, total triiodothyronine and free triodothyronine were assayed in 29--otherwise healthy--patients with pulmonary tuberculosis before initiation of anti-tuberculosis treatment and after two weeks of therapy. Twenty seven out of 29 patients presented low-normal total triiodothyronine levels, showing a statistical elevation after anti-tuberculosis therapy. Total triiodothyronine levels before anti-tuberculosis therapy were inversely correlated with levels of serum soluble interleukin-2 receptors. Further investigation on the relationship between soluble interleukin-2 receptor's levels and thyroid hormones in non-thyroidal disease can be envisaged.

Possible Role of Granulocyte Colony-Stimulating Factor in Increased Serum Soluble Interleukin-2 Receptor-α Levels After Allogeneic Bone Marrow Transplantation

Serum soluble interleukin-2 receptor - α (sIL-2R) levels markedly increased at the engraft-ment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, beacuse in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.

CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging.

Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR upregulation on T-lymphocytes. We further investigated this activation, by measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that constituted 8% of total lymphocytes, increased twofold with age and included CD4+, CD8+, and CD45RA+ phenotypes. HLA-DR was also expressed on a CD8+ CD57+ subset. The CD3+ CD25+ subset constituted 13% of lymphocytes, fell with age but was weakly associated with the CD3+ HLA-DR+ subset especially in older subjects. A small 3-5% CD3+ CD69+ subsets showed no age effect. Serum sIL-2R, TNF-alpha, but not IFN-gamma, were associated with CD3+ HLA-DR+ lymphocytes, TNF-alpha with CD8+ CD57+ count and sIL-2R and IFN-gamma with the CD3+ CD25+/CD3+ CD4+ ratio. The study confirms age-related upregulation of HLA-DR on CD3+ lymphocytes, shows some evidence for associated upregulation of CD25 on CD3+ cells in older subjects, and links serum TNF-alpha, IFN-gamma, and sIL2-R to T-lymphocyte activation.

Serum immunoglobulin and soluble IL-2 receptor levels in small intestinal overgrowth with indigenous gut flora.

Murine studies have demonstrated that the presence of indigenous gut flora is crucial for the induction of systemic immune hyporesponsiveness to antigens initially encountered within the gastrointestinal lumen. This study investigated whether increased titers of such flora, as occur in human small intestinal bacterial overgrowth, may be associated with increased suppression of systemic immune responsiveness and the possible relation between systemic and mucosal immunity in this setting. Serum total immunoglobulin (Ig), immunoglobulin subclass, and soluble interleukin-2 receptor levels and lamina propria IgA plasma cell counts were determined in 50 consecutive subjects with (N = 30) and without (N = 20) small intestinal bacterial overgrowth. Luminal IgA levels were measured in 35 of these subjects. Serum concentrations of IgG3, but not of other immunoglobulin isotypes or soluble interleukin-2 receptors, were significantly reduced in subjects with bacterial overgrowth (P < 0.0005). Small intestinal lamina propria IgA plasma cell counts (P < 0.0005) and luminal IgA concentrations (P = 0.001) were significantly increased in this group. Serum IgG3 levels were significantly inversely correlated with luminal IgA levels (P < 0.01) and fell below the lower limit of normal (0.41 g/liter) in 17/30 (56.7%) subjects with bacterial overgrowth compared to 1/20 (5.0%) subjects without (P < 0.0005). These findings document an association between small intestinal bacterial overgrowth with indigenous gut flora and reduced serum IgG3 reactivity in humans, possibly via an interaction with mucosa-related immunoregulatory mechanisms. The possibility of underlying small intestinal bacterial overgrowth should be considered in patients with serum IgG3 deficiency, especially those with compatible symptoms and/or known predisposition.

Clinical Significance of Serum Soluble Interleukin-2 Receptor Level in Patients with Non-Hodgkin's Lymphoma

Clinical Significance of Serum Soluble Interleukin-2 Receptor Level in Patients with Non-Hodgkin's Lymphoma

Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer

The level of the acute-phase response is a major predictor of survival in patients with advanced pancreatic cancer. This study examines the association between the acute-phase protein response, as determined by serum C-reactive protein, and serum levels of interleukin-6, soluble interleukin-6 receptor and the soluble tumour necrosis factor receptors in patients with pancreatic cancer. Thirty-four blood samples were collected from 13 patients with advanced pancreatic cancer. Samples were also collected from six healthy subjects. Levels of C-reactive protein, interleukin-6, soluble interleukin-6 receptor and soluble tumour necrosis factor receptors 55 and 75 were measured by indirect ELISA. Serum levels of C-reactive protein, interleukin-6 and soluble tumour necrosis factor receptors 55 and 75 were significantly higher in cancer patients than in controls. Levels of serum soluble interleukin-6 receptor were not significantly different between the two groups. In cancer patients, a significant positive association was found between the level of the acute-phase protein response and serum levels of interleukin-6, soluble tumour necrosis factor receptor 55 and soluble tumour necrosis factor receptor 75. No association was found between levels of soluble interleukin-6 receptor and any other factor. There is no significant relationship between the level of soluble interleukin-6 receptor and the acute-phase protein response in vivo and the biological role of soluble interleukin-6 receptor in the chronic inflammatory component of cachexia remains unclear.

Effects of hemoperfusion with polymyxin B-immobilized fibre on serum neopterin and soluble interleukin-2 receptor concentrations in patients with septic shock

the aim of the present study was to determine whether serum neopterin and soluble interleukin (IL)-2 receptor levels were related to the development of septic shock and whether polymyxin B-immobilized fibre (PMX-F) treatment affects these levels. we examined 24 patients admitted to our intensive care unit with Gram-negative septic shock. Serum neopterin and soluble IL-2 receptor levels were measured using commercially available test kits. Patients were treated with direct hemoperfusion using PMX-F columns. fifteen out of 24 patients (63%) survived and were discharged from our hospitals within 30 days after PMX-F treatment. Blood endotoxin levels decreased significantly from 49.2+/-8.6 pg/ml to 13.2+/-4.4 pg/ml after PMX-F treatment. The pretreatment serum concentrations of neopterin and IL-2 receptor were significantly higher in the nine non-surviving patients with septic shock than in the 15 surviving patients (P<0.01) and 20 control subjects (P<0.001). Serum concentrations of neopterin and IL-2 receptor in patients with septic shock decreased significantly after PMX-F treatment (P<0.01). these data suggest that serum neopterin and IL-2 receptor concentrations may be prognostic indicators in patients with septic shock. PMX-F treatment may be effective for reducing serum neopterin and IL-2 receptor concentrations.

A case of primary cardiac lymphoma: Utility of serum soluble interleukin-2 receptor for noninvasive diagnosis

A 70-year-old woman was referred to us for the investigation of a tumor mass in the right sided of the heart. LDH and soluble interleukin-2 receptor (sIL2r) were elevated. She died one day after the initiation of radiation therapy because of intractable cardiogenic shock. Primary cardiac lymphoma was identified at autopsy. Measurement of serum sIL2r lead us to the antemortem diagnosis of the disease.

Clinical implication of serum sIL-2R levels in ovarian cancer.

The levels of serum soluble interleukin-2 receptor (sIL-2R) of 36 patients with ovarian cancer, 34 with benign gynecological tumors and 31 blood donors were measured by ELISA. Compared to those of benign and normal controls, serum levels of sIL-2R in patients with ovarian cancer elevated significantly (P < 0.01). Serum sIL-2R levels were likely related to types, clinical stage or histological grading of ovarian cancer. We were led to conclude that serum sIL-2R level may reflect the status of the immune system and the disease severity in patients with ovarian cancer. Its value as a marker for monitoring treatment and prognosis needs further studies.