Soluble Interleukin-2 Receptor Concentrations Research Articles

Proinflammatory cytokines in acute asthma

Cytokine-mediated interactions between monocytes/macrophages, lymphocytes, and eosinophils may be important in regulation of airway inflammation in asthma. Peripheral blood cytokine concentrations were measured in twenty adults with severe, acute asthma, ten with mild asthma (intermittent inhaled beta-agonists), twelve with chronic asthma (high-dose inhaled steroids), and in sixteen healthy subjects. Interleukin-1 β, tumour necrosis factor, and interferon γ were not detected in most subjects. Granulocyte macrophage colony-stimulating factor concentrations were higher in patients with severe asthma than in healthy subjects (median 179 vs 80 pg/ml; 95% confidence interval for difference 16-168; p=0·009). Plasma concentrations of soluble interleukin-2 receptor (sIL-2R) were similar in all asthma groups (geometric mean in severe acute group 570 U/ml, mild group 559 U/ml, and chronic group 560 U/ml) and higher than those in healthy controls (361 U/ml, p<0·01). Sequential slL-2R measurements were done in fifteen of the patients with severe acute asthma. There was no difference between baseline concentrations and those after 2 days of steroid treatment but by day 7 they had fallen significantly (ratio day 7/day 3=0·74, [95% Cl 0·67-0·82]; p < 0·001); however, there was no correlation with improvement in peak expiratory flow. This study provides further evidence for T-lymphocyte activation in asthma but shows that plasma sIL-2R is not a useful marker of disease activity.

The relationship between nutritional status and serum soluble interleukin-2 receptor concentrations in patients with Crohn's disease treated with elemental diet

Serum soluble interleukin-2 receptor concentrations (sIL-2R) were measured and correlated with indices of disease activity and nutrition in 13 patients with active Crohn's disease treated with an elemental diet. The initial serum sIL-2R concentrations were raised, 1121 ± 181 U/ml (mean ± SEM) compared to controls, 177 ± 22.9 U/ml (n = 18) (p < 0.001). Four weeks' treatment resulted in significant improvement in disease activity (Harvey-Bradshaw index) and 4-day faecal 111Indium-leucocyte excretion. Serum sIL-2R concentrations did not change significantly after treatment, 789 ± 79.8 U/ml (p > 0.05). Serum sIL-2R concentrations were inversely correlated with albumin, pre-albumin, creatinine-height index and total body potassium. Only those patients with markedly elevated sIL-2R concentrations (>800 U/ml) and severe nutritional depletion prior to treatment, showed significant reductions in sIL-2R levels with elemental dietary treatment. These results demonstrate an association between nutritional impairment and immune activation in Crohn's disease.

Increased concentrations of soluble interleukin-2 receptor in the serum of patients with systemic sclerosis.

Increased concentrations of soluble interleukin-2 receptor in the serum of patients with systemic sclerosis.

Recovery of the small intestine in coeliac disease on a gluten‐free diet: Changes in intestinal permeability, small bowel morphology and T‐cell activity

Intestinal permeability was assessed before and 1, 2, 4, 8 and 12 weeks after commencing a gluten-free diet (GFD) in eight coeliac subjects. Intestinal morphology was quantified in six coeliac subjects on a normal diet, six coeliac subjects on a GFD, and 21 normal subjects. T-cell activity was measured in the eight coeliac subjects by soluble interleukin-2 receptor (sIL-2R) concentration (normal less than 477 U/mL). Intestinal permeability was increased 10-fold with a geometric mean value of 0.72 on a normal diet, and decreased to 0.17 at 4 weeks (P = 0.04), to 0.07 at 8 weeks (P = 0.010), and to 0.20 at 12 weeks (P = 0.015) of a GFD. Two of the eight subjects showed a poor response to gluten withdrawal. Quantitative intestinal morphology showed no significant improvement after 3 to 6 months of a GFD. Mean +/- s.d. sIL-2R concentrations in the eight subjects were increased 5-fold higher than control values at 1400 +/- 530 U/mL on a normal diet and decreased to 750 +/- 200 U/mL after 12 weeks of a GFD (P = 0.004). We conclude that intestinal permeability improves rapidly in the majority of coeliac subjects after commencing a GFD, although some abnormal permeability and increased T-cell activity persists. This may be due to varying degrees of gluten ingestion resulting in continued immune activation.

Soluble interleukin-2 receptor and soluble CD8 antigen in active rheumatoid arthritis

Concentrations of soluble interleukin-2 receptor (sIL-2R) and of soluble CD8 antigen (sCD8) in sera and in supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) derived from patients with active rheumatoid arthritis (RA) were studied. sIL-2R concentrations in sera derived from patients with RA (1484 ± 382 U/ml) were significantly higher than in sera derived from healthy controls (380 ± 110 U/ml; P < 0.0005). In contrast, supernatants of PHA-stimulated PBMC derived from patients with RA contained similar amounts of sIL-2R (727 ± 467 U/ml) as those derived from healthy control individuals (833 ± 508 U/ml; P > 0.1). When investigated for the presence of sCD8 antigen, sera derived from patients with RA contained significantly lower amounts (30 ± 28 U/ml) than sera derived from healthy controls (405 ± 136 U/ml; P < 0.0005). Similarly, PHA stimulation of PBMC derived from patients with RA resulted in a significantly lower production of sCD8 (35 ± 46 U/ml) as compared to the one obtained by PHA stimulation of PBMC derived from healthy controls (177 ± 59 U/ml; P < 0.0005). This difference could not be explained by a lower proliferative response to PHA by PBMC derived from patients with RA (21,474 ± 14,022 cpm) as compared to healthy controls (29,549 ± 11,188 cpm; P > 0.05). Our data demonstrate that PBMC derived from patients with active RA differ from PBMC derived from healthy individuals concerning their ability to produce sIL-2R and sCD8.

Soluble interleukin‐2 receptors in children with kawasaki syndrome

We studied levels of soluble interleukin-2 receptors (IL-2R) in serial serum samples obtained from 93 patients with Kawasaki syndrome, using a double-antibody "sandwich" enzyme-linked immunosorbent assay technique. Concentrations of soluble IL-2R were significantly increased in Kawasaki syndrome patients in the first 4 weeks of illness when compared with either healthy adult or pediatric controls (P less than 0.02), and in the first 2 weeks of illness when compared with a group of children with measles (P less than 0.0001). Furthermore, in the second week of illness, levels of soluble IL-2R were significantly greater in children who subsequently developed coronary artery aneurysms than in patients with normal appearing coronary arteries. Serum concentration of soluble IL-2R is a useful marker for detecting early Kawasaki syndrome and identifies those patients who are at greater risk of developing coronary artery aneurysms.

Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.

Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease.

T-cell activation in Crohn's disease: Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells

Serum levels of soluble interleukin-2 receptor were determined in 29 patients with active and quiescent Crohn's disease. In addition, the ability of peripheral blood mononuclear cells of 23 of these patients to generate soluble interleukin-2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin-2 receptor concentrations of patients with active Crohn's disease (n = 19) were significantly elevated (757 ± 438 U/ml) compared with levels in patients with inactive disease (n = 10; 412 ± 120 U/ml) and healthy control individuals (n = 40; 375 ± 102 U/ml; p < 0.003 and p < 0.0005, respectively). Serial determinations of serum soluble interleukin-2 receptor concentration in a follow-up of 11 hospitalized patients treated for highly active disease showed a decrease from 1252 ± 494 U/ml to 527 ± 193 U/ml (p < 0.004) that corresponded to clinical improvement, as assessed by Crohn's disease activity index and a reduction of inflammatory parameters. In vitro phytohemagglutinin stimulation of peripheral blood mononuclear cells derived from patients with Crohn's disease resulted in elevated soluble interleukin-2 receptor production not only in patients with active disease (3987 ± 2439 U/ml), but also in patients with inactive disease (3297 ± 2282 U/ml), compared with the amount of soluble interleukin-2 receptor produced by mononuclear cells of healthy individuals (1523 ± 1152 U/ml; p < 0.005 and p < 0.02, respectively). In addition, cultivation of mononuclear cells without mitogen resulted in higher soluble interleukin-2 receptor production in patients with active disease than in patients with inactive disease (p < 0.02). However, patients suffering from active ulcerative colitis also had significantly increased serum levels of soluble interleukin-2 receptor (1080 ± 400 U/ml) compared with the levels in patients with chronic disease (455 ± 140 U/ml; p < 0.0025). In addition, peripheral blood mononuclear cells derived from patients with ulcerative colitis produced significantly more soluble interleukin-2 receptor upon mitogenic stimulation with phytohemagglutinin (2314 ± 936 U/ml), than cells from healthy controls (1523 ± 1152 U/ml; p < 0.05). The finding of elevated soluble interleukin-2 receptor serum levels in patients with active Crohn's disease and its increased production by mononuclear cells of patients with both active and inactive disease is a further example of an alteration of the immune system in this condition; however, this alteration can also be found in other inflammatory bowel diseases.

T cell activation in Guillain‐Barré syndrome and in MS

Guillain-Barré syndrome (GBS), chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS) are disorders with presumed immunopathogenesis. To obtain evidence for T cell activation, we determined serum concentrations of soluble interleukin-2 receptors (sIL-2 R) in 50 patients with GBS, 24 with CIDP, and 54 with MS. Both in GBS and clinically active MS sIL-2 R levels were markedly increased compared with those in patients with other neurologic diseases. Four of 24 CIDP patients had abnormally increased sIL-2 R concentrations. sIL-2 R concentrations decreased with clinical improvement in serial samples taken from GBS patients, but were not otherwise correlated with disease severity. These data establish that T cells are activated in GBS and some patients with CIDP, and corroborate earlier evidence that activated T cells are circulating in the blood of MS patients.

Activation of lymphocytes induced by recombinant human granulocyte- macrophage colony-stimulating factor in patients with malignant lymphoma

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high- dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

Activation of Lymphocytes Induced by Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Malignant Lymphoma

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high-dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

Serum Soluble Interleukin-2 Receptor in Patients with Glomerulonephritis

Serum soluble interleukin-2 receptor (IL-2R) concentrations were determined using the ELISA method in 55 cases of glomerulonephritis. These patients can be classified as 29 cases of IgA nephropathy, 10 cases of membranous glomerulonephritis and 16 cases of mesangial proliferative glomerulonephritis. Our results showed that serum soluble IL-2R concentrations in glomerulonephritis cases were significantly higher than those in healthy controls. Among the different types of glomerulonephritis cases, however, no significant differences in serum soluble IL-2R were observed. While we found a significant positive correlation of serum soluble IL-2R to BUN and creatinine, we also found a significant negative correlation between serum soluble IL-2R and creatinine clearance. These findings suggest that serum soluble IL-2R can serve as an indicator of exacerbation of glomerulonephritis.

Plasma elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise.

The effects of a 2.5-h running test on the plasma concentrations of elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor were evaluated in eight healthy young male subjects. Neopterin was measured by radioimmunoassay, elastase-alpha 1-antitrypsin, tumor necrosis factor, and soluble interleukin-2 receptor by enzyme immunoassay. The post-exercise values were corrected for plasma volume changes which were calculated from hematocrit and hemoglobin values. Compared with the concentrations before exercise, elastase-alpha 1-antitrypsin values were significantly increased during the run (1 h after the start) (P less than 0.01) as well as during the first few hours after the end of the running test (P less than 0.01). A significant increase of tumor necrosis factor and neopterin was observed 1 h after the end and 1,3, and 24 h after the end of the running test, respectively, (P less than 0.01), and soluble interleukin-2 receptor concentrations were significantly elevated 1 and 2 days after exercise (P less than 0.01). The increase of elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor supports the concept of a functional involvement of polymorphonuclear neutrophils and an activation of macrophages and T-lymphocytes after prolonged exercise.

Relation between soluble interleukin 2 receptor and clinical findings in patients with systemic lupus erythematosus.

The concentration of soluble interleukin 2 receptor (IL-2R) was determined in the serum of 54 patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay (ELISA) using two monoclonal antibodies with the IL-2R. Concentrations of soluble IL-2R in the serum of the patients with SLE (study group) were significantly higher than in 20 normal subjects (control group). The relation between concentrations of soluble IL-2R and clinical findings was investigated. The concentration of soluble IL-2R showed no particular relation with the clinical manifestations and did not correlate with the level of anti-DNA antibody or CH50. Significant correlation between the concentration of soluble IL-2R and disease activity did exist, however. Furthermore, the concentration of soluble IL-2R in some cases changed simultaneously with the disease activity. Thus the concentration of soluble IL-2R may serve as a new clinical indicator of disease activity in patients with SLE.

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.

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.