Soluble interleukin-2 receptor in sera of patients with Graves' disease.

Recently, in vitro production of interleukin-2 receptor induced by mitogens have been shown to be impaired in autoimmune disorders including organo-specific autoimmune diseases. The aim of this study was to investigate serum levels of soluble interleukin-2 receptor in 20 untreated patients with Graves' disease and to follow up their changes in relation to clinical picture and TSH-receptor-, anti-thyroglobulin-, anti-microsomal as well as anti-eye muscle antibodies. Soluble interleukin-2 receptor level was significantly increased in newly-diagnosed Graves' patients compared to controls (667 +/- 270 vs. 205 +/- 45 U/ml) (P less than 0.001). Among the patients sera those with active infiltrative ophthalmopathy had higher soluble interleukin-2 receptor levels than those without eye symptoms (810 +/- 313 vs. 525 +/- 180 U/ml). Soluble interleukin-2 receptor level was normalized in Methimazole-treatment-induced remission in the majority of patients except those with ophthalopathy. In five patients the soluble interleukin-2 receptor levels were studied after interruption of thyrostatic therapy; an increase was observed in three patients; thereafter hyperthyrosis relapsed in two cases. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies, however, the association with other immune parameters examined was not significant. In conclusion, an enhanced level of soluble interleukin-2 receptor was detected in patients with untreated Graves' disease. This finding might play a significant role in regulation of impaired cell-mediated immune mechanism and has a prognostic value for relapse of autoreactive processes.     

The balance shift in Th1/Th2 related IL-12/IL-5 cytokines in Graves' disease during methimazole therapy

Th1 and Th2-like cytokines are involved in the pathogenesis of Graves' disease. The shift in balance in IL-12/IL-5 cytokines was applied in judging the immunological events in 74 patients with Graves' disease (50 had ophthalmopathy) during methimazole therapy and in 15 controls. The serum levels of IL-12 and IL-5 were measured with enzyme-linked immunosorbent assay in all Graves' patients. Twelve cases for IL-5 and 20 cases for IL-12 were positive. In Graves' patients only those without ophthalmopathy had higher levels of IL-12 when compared to controls (192.66 +/- 29.19 vs. 85.09 +/- 8.95 pg/ml, P < 0.04). After 2 months of methimazole therapy in Graves' patients without ophthalmopathy an increase in the ratio of IL-12 to IL-5 was also observed as compared to those with eye symptoms (91.78 +/- 34.14 vs. 20.72 +/- 6.36, P < 0.015). Age-related difference in the serum level of IL-5 could be demonstrated between Graves' patients without and those with ophthalmopathy aged < or = 35 years (4.89 +/- 0.57 vs. 50.14 +/- 20.2 pg/ml, P < 0.002). No association was found among the serum levels of IL-5 or IL-12, thyroid hormones and TSH receptor antibodies. The results demonstrated a difference in the balance shift of IL-12/IL-5 between Graves' patients with and without ophthalmopathy. The increased ratio of IL-12 to IL-5 after methimazole therapy could be explained by the elevation of serum IL-12 due to methimazole therapy and the age-related decrease of serum IL-5.     

Soluble interleukin-2 receptors in plasma cell dyscrasias

Levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 69 patients with plasma cell dyscrasias. A close relationship was seen between serum sIL-2R levels and clinical features. Among patients with normal BUN and creatinine levels, the mean (+/- 1SD) level of sIL-2R in 44 patients with multiple myeloma (MM) was higher than that of normal controls (457 +/- 227 U/ml vs 288 +/- 124 U/ml, P = 0.01). The mean level of sIL-2R in eight patients with primary macroglobulinemia was 722 +/- 251 U/ml. In MM, those with active or refractory disease showed a significantly higher mean level of sIL-2R than those in the remission phase (577 +/- 240 U/ml vs 335 +/- 103 U/ml, P = 0.01). There was a negative correlation between sIL-2R and hemoglobin levels in MM patients (r = -0.45, P = 0.01). Five patients with complications of renal insufficiency had elevated levels of sIL-2R. In a longitudinal study of a patient with plasmacytoma and an extremely high sIL2-R level, the sIL-2R level showed a strong relationship with tumor burden. Patients with high sIL-2R levels generally had a poor prognosis than those with normal levels. Thus a high sIL-2R level may be an indicator of a poor prognosis in MM.     

Soluble IL-2 receptor levels in patients with Graves'' ophthalmopathy.

In various autoimmune diseases circulating levels of soluble IL-2 receptor (sIL-2R) seem to be related to disease activity. Because reliable parameters of disease activity in Graves' ophthalmopathy are lacking, we measured sIL-2R levels in 47 patients with this disorder. The patients had Graves' disease, but no other immune-mediated diseases, had not yet received specific treatment for their ophthalmopathy and were euthyroid during the entire study period. Twenty-one of the 47 patients (45%) had sIL-2R values above the upper normal limit of 650 U/ml, as established in 20 healthy controls. There were no differences between patients with normal (median 469, range 280-644 U/ml) and elevated (median 946, range 678-1588 U/ml) sIL-2R levels regarding duration or severity of the eye disease (as assessed clinically from the total eye score). However, patients with severely enlarged eye muscles had higher sIL-2R values than patients with less severely enlarged eye muscles on CT scan. Patients with elevated sIL-2R tended to have a higher response rate (71%) to a 3-month course of prednisone, than those with normal levels (46%; P = 0.081). Since a successful outcome of prednisone treatment might be representative for disease activity, the elevated sIL-2R levels seem to reflect active inflammation. Although the practical relevance of this finding in individual patients is limited, it underscores the importance of cell-mediated immune responses in this thyroid-related eye disease.     

Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker in the treatment of thyrotoxicosis.

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 +/- 1.5 ng/ml; week 2, 10.8 +/- 1.2 ng/ml; week 4, 8.9 +/- 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 +/- 1.4 ng/ml; week 2, 12.3 +/- 1.3 ng/ml; week 4, 10.9 +/- 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.     

Zinc supplementation stimulates tetanus antibody formation and soluble interleukin-2 receptor levels in chronic hemodialysis patients

Summary Immunodepression in end-stage renal disease has been associated with zinc deficiency. In a controlled study serum zinc levels, serum concentrations of soluble interleukin-2 receptor (sIL-2R), and tetanus IgG antibody titers were measured in 65 hemodialysis patients before and after intravenous zinc supplementation for 2 months. The hemodialysis patients had significantly lower predialysis serum zinc concentrations compared to healthy controls (63 ± 1.65 versus 126 ± 4.6 g/dl, P < 0.001). Serum zinc concentrations increased to the normal range in the zinc-treated patients. After zinc substitution tetanus antibody titers rose significantly (0.81 ± 0.12 versus 1.22 ± 0.12U/ml, P < 0.01). Pretreatment sIL-2R levels were elevated in 95% of examined patients. A further increase in sIL-2R was observed after zinc supplementation (234 ± 14 versus 285 ± 21 U/ml, P<0.05). The results suggest that zinc induces the activation of T lymphocytes and T-cell dependent B lymphocytes in chronic uremic patients in vivo.Abbreviations IL-2 interleukin-2 - sIL-2R soluble interleukin-2 receptor     

Plasma soluble interleukin-2 receptor (sIL-2R) levels in patients with acute leukemia

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.     

Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their incidence, significance and clinical usefulness

The incidence and the significance of TSH-receptor antibodies in Graves' disease and in various thyroid disorders have been evaluated. TSH-binding inhibiting antibodies (TBIAb) and thyroid stimulating antibodies (TSAb) were detected in a large proportion of Graves' disease patients (TBIAb in 68.8% and TSAb in 77.8%), in a small number of patients with idiopathic myxoedema or Hashimoto's thyroiditis, and were not detected in patients with endemic euthyroid goitre, differentiated thyroid carcinoma and toxic adenoma. Furthermore, TSH-receptor antibodies were present in some patients with toxic multinodular goitre (TBIAb in 12.7% and TSAb in 15.9%). When TSH-receptor and other thyroid autoantibodies were compared, it was found that 13 of the 15 Graves' patients with negative tests for thyroglobulin and thyroid microsomal antibodies were positive for TSH-receptor antibodies. On the other hand, 9 of the 11 patients with toxic multinodular goitre who had positive TSH-receptor antibody tests, also had serum thyroglobulin and/or thyroid microsomal antibodies. No significant differences in the prevalence of TSH-receptor antibodies were found in Graves' patients irrespective of the presence of ophthalmopathy or pretibial myxoedema. Elevated TBIAb activity at the end of anti-thyroid drug treatment was found in 52.9% of Graves' patients who subsequently relapsed, while in Graves' patients in remission TBIAb was always negative. TSH-receptor antibody results were not predictive of the outcome of radioiodine treatment in Graves' disease. Finally no correlation could be found between TBIAb and TSAb in Graves' disease and Hashimoto's thyroiditis. In conclusion: the high incidence of TSH-receptor antibodies in Graves' disease confirms their pathogenetic role in the development of hyperthyroidism; TSH-receptor antibodies in Graves' disease are not significantly associated with the presence of ophthalmopathy or pretibial myxoedema; TSH-receptor antibody assays may be useful for the diagnosis of Graves' disease in the absence of other signs of autoimmunity. TBIAb seems to be a good predictor of relapse in Graves' patients treated with anti-thyroid drugs; a fraction of toxic multinodular goitre could be a nodular variant of Graves' disease.     

他巴唑对Graves病患者血清可溶性白细胞介素—6受体的影响

５２例Ｇｒａｖｅｓ病（ＧＤ）患者随机分两组,２６例接受他巴唑（ＭＭＩ）、另２６例接受ＭＭＩ加心得安治疗。应用酶联免疫吸附分析（ＥＬＩＳＡ）,测定了未治疗期（第０周）,部分缓解期（第２周）和缓解期（第６周）患者及２０名健康对照者血清可溶性白细胞介素－６受体（ｓＩＬ－６Ｒ）水平。     

巨细胞病毒感染与可溶性白细胞介素2受体的关系

应用酶联免疫吸附试验（ＥＬＩＳＡ）对１０４例育龄妇女的血清进行了巨细胞病毒（ＨＣＭＶ）ＩｇＧ、ＩｇＭ抗体的检测，同时用ＥＬＩＳＡ双抗体夹心法测定了不同感染状态下血清中可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）的水平，并将ｓＩＬ－２Ｒ水平与未感染ＨＣＭＶ的正常育龄妇女进行了比较。结果，育龄妇女中抗－ＨＣＭＶＩｇＧ的阳性率为８９．４％，ＩｇＭ的阳性率为９．６％，感染ＨＣＭＶ的妇女血清中ｓＩＬ－２Ｒ水平均大于未感染的对照组（１７８．１±５７．３Ｕ／ｍｌ），Ｐ＜０．０５，其中ＩｇＭ阳性者和ＩｇＭ、ＩｇＧ同时阳性者血清中ｓＩＬ－２Ｒ水平最高，分别为９１０±４６５．６Ｕ／ｍｌ和９０５±３４７．８Ｕ／ｍｌ，两者间的差异无显著性意义（Ｐ＞０．０５），但均大于仅抗－ＨＣＭＶＩｇＧ阳性者（４４６．８±１５８．９Ｕ／ｍｌ），Ｐ均＜０．０５。表明，ＨＣＭＶ感染可致ｓＩＬ－２Ｒ水平升高，并且活动性感染者上升明显。提示：ｓＩＬ－２Ｒ可能参与了ＨＣＭＶ的免疫致病机制。     

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 less than 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 greater than 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 less than 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 less than 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 greater than 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.     

Increased serum soluble Fas ligand in hyperthyroid Graves' disease

The interaction of Fas with its ligand (FasL) regulates a number of physiological and pathophysiological process of cell death or apoptosis. Recent studies suggest that Fas and Fas ligand (FasL) interactions among thyrocytes from patients with Hashimoto disease which is caused by thyroid autoimmunity may contribute to clinical hypothyroidism. The role of Fas-FasL interaction in the pathophysiology of Graves' disease has not well been determined. The serum levels of soluble Fas (sFas) and FasL (sFasL) were measured in 48 Japanese patients with Graves' disease (U; untreated hyperthyroidism, T; hyperthyroidism under treatment, E; euthyroidism under treatment and R; remission), destructive thyroiditis (D), subacute thyroiditis (S) and 40 normal controls using commercially available ELISA kits. The levels of sFas (mean +/- SD, ng/ml) were 0.93 +/- 0.30 in normal controls (n = 32), 2.41 +/- 1.28 in U (n = 19), 2.44 +/- 0.79 in T (n = 16), 2.37 +/- 0.55 in E (n = 12), and 2.30 +/- 0.11 in R (n = 6), 2.42 +/- 0.37 in D (n = 3) and 2.68 +/- 0.17 in S (n = 3). There were no significant differences of sFas levels among any groups. While, the mean levels of sFasL (ng/ml) of normal controls were 0.058 +/- 0.02 (n = 40), and those of patients with hyperthyroid Graves' disease (U; 0.34 +/- 0.09 and T; 0.26 +/- 0.05), were significantly higher than those in normal controls (p < 0.005) and with subacute thyroiditis (0.097 +/- 0.001, vs U; p < 0.01, vs T; p < 0.05) but not different from those in E, R and D (E; 0.34 +/- 0.09, R; 0.25 +/- 0.07 and D; 0.31 +/- 0.11, respectively). There was a significant correlation between serum thyrotropin receptor antibody (TRAb) and free thyroxine levels (p < 0.01) while there were no correlation between sFas and sFasL levels and TRAb or free thyroxine levels. The results indicate that the Fas-FasL system contributes to the pathophysiology of hyperthyroid Graves' disease although serum sFas and sFasL levels do not appear to be useful indicators in evaluating disease activity.     

Soluble interleukin-2 receptor and interleukin-4 in sera of asthmatic children before and after a prednisolone course.

BACKGROUND: Cytokine-mediated interactions among inflammatory cells may play a role in the pathogenesis of bronchial asthma. OBJECTIVE: To understand the role of soluble interleukin-2 receptor (sIL-2R) and interleukin-4 (IL-4) in the disease activity of acute asthma, changes in serum concentrations of sIL-2R and IL-4 elaborated by activated T-lymphocyte before and after prednisolone therapy with clinical improvement were determined in the present study. METHODS: Circulating levels of sIL-2R and IL-4 in sera from 15 normal control subjects and in sera from 20 allergic asthmatic children with acute exacerbation and in a stable condition were determined by using commercially available ELISA kits. RESULTS: The mean concentration of serum sIL-2R was significantly higher in acute exacerbation than in children with stable asthma (368.9 +/- 395.4 pg/mL vs 291.2 +/- 361.0 pg/mL; P < .01) or in control subjects (124.6 +/- 17.8 pg/mL; P < .001). The mean concentration of serum IL-4 was higher in acute exacerbation (5.82 +/- 1.10 pg/mL) and in stable asthmatic patients (6.73 +/- 2.83 pg/mL) versus control group subjects (5.54 +/- 1.20 pg/mL). However, the difference was not statistically significant among the three study groups. CONCLUSIONS: This study provides further evidence that changes in serum IL-2R may serve as an objective indicator for clinical outcome of allergic asthmatic patients.     

Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers

The levels of soluble IL-2Ralpha (sIL-2Ralpha) in serum were measured in HTLV-1 carriers and ATL patients in order to evaluate their possible correlation with clinical status. Mean sIL-2R levels in ATL patients were found to be 9704 U/ml for the acute/lymphoma type, 1961 U/ml for the chronic type and 788 U/ml for the smouldering type. The level for asymptomatic HTLV-1 carriers was 475 U/ml, and 165 U/ml for healthy young adult HTLV-1- controls. The serial measurement of sIL-2R in ATL patients, healthy HTLV-1 carriers, and HTLV-1 carriers with diseases other than ATL showed a good correlation between serum levels of sIL-2R and the pathophysiological status of disease. Furthermore, an increase in the sIL-2Ralpha level in serum indicated the exacerbation of HTLV-1 infection and autoimmune diseases. The measurement of sIL-2Ralpha levels is therefore a very useful parameter for determining disease status.     

Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.     

Serum markers of T cell activation in relapses of Wegener's granulomatosis.

Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.     

Cytokines serum levels as the markers of thyroid activation in Graves'' disease

In order to examine which cytokine could be used as a marker of the biological effect of thyroid hormones or anti-thyroid antibodies in Graves' disease (GD) patients, we simultaneously evaluated the concentrations of TSH, free thyroid hormones (fT₃ and fT₄), anti-thyroid antibodies (anti-TPO and anti-TG) and a group of cytokines: interleukin-2 (IL-2), tumour necrosis factor (TNF), interleukin-6 (IL-6) and their soluble receptors (sIL-2R, sTNFR, sIL-6R) as well as interleukin-10 (IL-10) in eight GD females and nine normal controls. We found that serum sIL-2R concentrations of GD patients had only the tendency to be higher versus controls, but strong positive correlations between fT₃ and fT₄ and sIL-2R in peripheral blood of GD subjects were revealed. We showed that sIL-2R was the best cytokine marker, showing very good correlation with the endocrine status of GD patients.     

Soluble IL-2 receptor and tumour necrosis factor-alpha in plasma of haemophilia patients infected with HIV.

We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.     

Serum interleukin-2-receptor in coeliac disease: response to treatment and gluten challenge.

Concentrations of the soluble interleukin-2 receptor (sIL-2R) in the serum of 33 patients with coeliac disease were measured by ELISA. The levels of sIL-2R were significantly raised in 15 patients with untreated coeliac disease compared with treated patients and age- and sex-matched symptomatic and non-symptomatic control groups. Longitudinal studies in individual coeliac patients showed that serum sIL-2R fell following commencement of a gluten-free diet. Gluten challenge of 16 treated coeliac patients for 1 week resulted in a significant increase in serum sIL-2R, which returned to prechallenge levels within 4 weeks of recommencement of a gluten-free diet. We suggest that serum sIL-2R levels in patients with coeliac disease reflect specific immunological activation in response to gluten ingestion. Measurement of serum sIL-2R may therefore be useful in the assessment of response to treatment in patients with coeliac disease.     

The study of immunological markers in patients with "intrinsic" type atopic dermatitis]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by several clinical, immunological and biochemical alterations. Comparing the patients with the 'extrinsic' and 'intrinsic' types of AD, we investigated the role of immunological mechanisms in the pathogenesis of AD. To confirm it, we calculated serum markers of T lymphocyte activation: soluble interleukin-2 receptor (sIL-2R), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma). The soluble CD14 (sCD14) and tumor necrosis factor-alpha (TNF-alpha) in serum were measured as monocyte/macrophage activation markers. We examined 29 patients with the 'extrinsic' type AD (serum IgE > 10000 IU/ml: High-AD), 23 patients with the 'intrinsic' type AD (serum IgE < 37 IU/ml: Low-AD) and 11 healthy controls. Serum sIL-2R levels were increased in High-AD and Low-AD compared with the controls. They were also significantly increased in High-AD compared with Low-AD. Serum sCD14 levels were increased in High-AD compared with Low-AD and the controls. Severity index of AD were correlated with serum sIL-2R levels but not with sCD14 levels in sera. In conclusion, IgE may not relate with the pathogenesis of atopic dermatitis. Serum sIL-2R levels may be increased according to inflammatory skin lesions and it may be exaggerated with the immunological activation in the patients with the 'extrinsic' type AD.