Serum concentration of soluble interleukin-2 receptor as a sensitive parameter of disease activity in sarcoidosis

We investigated the clinical value of measuring serum concentrations of soluble IL-2R in monitoring sarcoidosis. Serum concentrations of soluble IL-2R were measured in 70 patients with sarcoidosis. The mean value for active untreated sarcoidosis was 1,143 +/- 509 U/ml, while the normal range in 97 healthy control subjects was 80 to 300 U/ml. The mean value for active untreated sarcoidosis was significantly higher than that for dormant disease (353 +/- 183 U/ml) or that for corticosteroid-treated patients (380 +/- 151 U/ml). Serial changes in serum soluble IL-2R level were studied in cases of spontaneous remission or in corticosteroid-treated patients; a good correlation was noted between the changes in serum level of soluble IL-2R and clinical status. A positive correlation was noted between serum concentration of soluble IL-2R and serum ACE activity. These data confirmed that measurement of serum concentration of soluble IL-2R could be used in monitoring the disease activity in sarcoidosis.     

Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus

Summary We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.     

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.     

Lack of association between hyperprolactinemia and soluble IL-2 receptor levels in systemic lupus erythematosus

The aim of the study was to evaluate the association between hyperprolactinemia and T lymphocyte activation through the soluble IL-2 receptor (sIL-2R) in systemic lupus erythematosus (SLE) patients. Seventy SLE patients, 18 of them with hyperprolactinemia (HPRL), were compared with 18 normoprolactinemic (NPRL) patients and 10 age-matched healthy blood-bank donor women. Patients were evaluated by means of the SLE activity index (SLEDAI). Total serum IgG and sIL-2R levels were determined by an ELISA assay. Differences between sIL-2R and IgG serum levels in patients and controls were examined by Kruskal-Wallis analysis and a Spearman r correlation to determine the association between sIL-2R, IgG and prolactin (PRL) levels. IgG and sIL-2R serum levels did not differ significantly between HPRL and NPRL patients: 1827.3 (1428-2226) vs 2028.8 (1586-2467) mg/dl and 882.2 (511-1254) vs 740.1 (534-946.4) U/ml, respectively (confidence interval 95%). In the total SLE group, sIL-2R and IgG serum levels were positively associated (P = 0.0009), however, this was not the case for sIL-2R and PRL (P > 0.49). We did not demonstrate an association between HPRL and lymphocyte activation measured through serum sIL-2R in female patients with SLE.     

Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.     

The relationship between soluble interleukin 2 receptor levels and antidouble stranded DNA antibody levels in patients with systemic lupus erythematosus

Levels of soluble interleukin 2 receptors (IL-2R) have been found to be elevated in the serum of patients with systemic lupus erythematosus (SLE) and are considered an indication of immune system activation in this disease. To assess the relationship between soluble IL-2R levels and other serological markers, we compared levels of soluble IL-2R and anti-double stranded DNA (anti-dsDNA) antibodies in SLE sera. In a cross sectional study of 34 patients with SLE, soluble IL-2R levels were elevated compared with healthy individuals (1126 U/ml vs 235 U/ml, p less than 0.0001), and a significant correlation between levels of soluble IL-2R and anti-dsDNA antibodies was present (r = 0.543, p = 0.0009). In a longitudinal study of 10 additional patients, the time courses of soluble IL-2R levels and anti-dsDNA antibody measurements were similar in 3 patients. In 7 patients, substantial differences in the levels of soluble IL-2R and anti-dsDNA antibodies over time were observed, including marked changes in anti-dsDNA antibody levels that were accompanied by only minor changes in soluble IL-2R levels, and soluble IL-2R measurements that were persistently elevated despite generally low anti-dsDNA antibody levels. Our results indicate that soluble IL-2R levels may not always parallel other serological markers of SLE, suggesting measurement of different facets of immune system activation by various assays.     

Increased serum β2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients

The objective of this study was to explore the relationship between serum levels of β2-microglobulin (β2MG), which some studies suggest reflect disease activity in systemic lupus erythematosus (SLE), and various clinical and immunological markers of disease activity in SLE. Twenty-six SLE patients and 10 healthy controls were included. Disease activity was assessed by: SLEDAI, 24?hr-proteinuria, circulating levels of complement C3, anti-double-stranded DNA (anti-dsDNA), β2MG and various pro-inflammatory and anti-inflammatory cytokines (IL-6, IL-8, IL-10, IL-18) measured with a multiplex assay, IFN-α assessed with a reporter gene assay, and a combined expression score of 12 IFN-α inducible genes in peripheral blood mononuclear cells. Median serum levels of β2MG were significantly higher in SLE patients vs controls (2.8?mg/L, range: 1.1-21.6 and 1.2?mg/L, range: 0.9-1.7, respectively, p?相似文献   

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

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

Relations between surface expression of the interleukin-2 receptor and release of the soluble form of the receptor in cultured mononuclear cells from patients with rheumatoid arthritis or systemic lupus erythematosus

The relationship between surface expression of the interleukin-2 receptor (IL-2R) and release of the soluble form of the receptor (sIL-2R or sCD25) was investigated with peripheral blood mononuclear cells (PBMCs) from individuals with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). The spontaneous release of sCD25 was significantly increased in PBMCs from RA patients and decreased in cells from SLE patients, compared with normal controls. However, the extent of sCD25 release from phytohaemagglutinin (PHA)-stimulated PBMCs did not differ between RA or SLE patients and normal controls. The serum concentration of sCD25 was significantly increased in SLE or RA patients compared with the normal controls. Whereas the surface expression of CD25 by unstimulated PBMCs did not differ among the three groups of subjects, this parameter was significantly reduced for PHA-stimulated PBMCs from RA patients relative to those from normal controls. The surface expression of CD25 showed a positive correlation with sCD25 release for PBMMCs from SLE patients under either basal or stimulated conditions. No such relation was apparent for cells from RA patients. The surface expression of IL-2R (CD122) under basal or stimulated conditions was significantly reduced in PBMCs from RA or SLE patients, compared with cells from normal controls. Thus, the increased concentration of sCD25 in the serum of individuals with these autoimmune rheumatic diseases may result from two different mechanisms: an increase in the spontaneous release of sCD25 in RA, and reduced clearance of this protein in SLE.     

Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines

OBJECTIVE: The aim of this study was to investigate the imbalance between Th-1 and Th-2 cytokines in systemic lupus erythematosus patients (SLE) and to asses if any of these cytokines could be related to disease activity. METHODS: Twenty SLE patients and 20 healthy individuals were investigated. Blood samples were collected to evaluate, using ELISA method, serum levels of a wide array of cytokines including: Th-1 type cytokines (Interleukin (IL)-12, Interferon (IFN)-gamma), Th-2 cytokines (IL-4, IL-10), pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, IL-1beta and IL-18). Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Data were evaluated using the Mann-Whitney and Spearman's rank tests. RESULTS: The SLE patients group had a higher IL-4, IL-10, IL-12 and IL-18 serum concentration compared to the normal control group. IL-18 was negatively correlated with IL-4 and positively correlated with IFN-gamma. No serum cytokine level was correlated with disease activity except for IL-18, which was found strongly correlated with "active disease", defined as SLEDAI > 8 points. IL-18 showed no correlation with pro-inflammatory cytokines. CONCLUSIONS: Our results show that Th-1 as well Th-2 cytokines can be elevated in SLE patients suggesting that lupus is a complex disease that may be supported by different cytokine patterns in different time-points. Only IL-18 has been found to be disease-activity related. The role of IL-18 in the pathogenesis of SLE might be important through apoptosis-mediating properties.     

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

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

Circulating angiogenesis inhibitor endostatin and positive endothelial growth regulators in patients with systemic lupus erythematosus

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4 pg/ml) than in inactive disease (118.1 pg/ml, P < 0.05) or in control group (133.5 pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2 pg/ml) than in the control group (252.7 pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (p = 0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (p = 0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (p = - 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.     

Cytokine production, serum levels and disease activity in systemic lupus erythematosus

OBJECTIVE: T cell abnormalities, B cell hyperactivity and abnormal cytokine production have been implicated to be of pathogenic importance in systemic lupus erythematosus (SLE). The aim of this study was to investigate if ongoing production and serum levels of type 1 and 2 cytokines reflect disease activity and the presence of organ manifestations. METHODS: Fifty-two SLE patients and 29 healthy individuals were investigated. Blood samples were collected for assessment of anti-ds DNA antibodies, cytokine production and serum cytokine levels. Disease activity was simultaneously assessed using the Systemic Lupus Activity Measure (SLAM) index and SLE Disease Activity Index (SLEDAI). ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC) was used to estimate the production of cytokines (gamma-interferon (IFN-gamma), interleukin-4 (IL-4), IL-6 and IL-10) using both unstimulated cells and cells stimulated with the T cell mitogen phytohaemagglutinin (PHA). Serum levels of IL-10 were determined using an ELISA method, serum levels of IL-6 were determined using a bioassay and anti-ds DNA antibodies were analysed by immunofluorescence. RESULTS: The SLE patient group had significantly increased numbers of cells spontaneously producing IL-10 and IL-6 as compared to healthy controls (P = 0.01 and 0.03, respectively). The number of cells producing IL-10 and IL-6 after PHA-stimulation was also increased in SLE patients (P = 0.01 and < 0.0004, respectively). Serum IL-10 and IL-6 levels were also significantly increased in SLE patients (P < 0.0004 and 0.0005, respectively). Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the patients. No correlation was found between disease activity or clinical profiles and the production or serum levels of cytokines except for a weak correlation (not statistically significant) between levels of IL-10 in the sera and disease activity as measured by the SLEDAI but not by the SLAM index. CONCLUSION: Our results confirm earlier reports that SLE patients have an increased production as well as increased serum levels of the type 2 cytokines IL-10 and IL-6. We found no significant correlation between IL-6 and IL-10 and disease activity or clinical profiles. Serum IL-10 levels correlated with the titre of anti-ds DNA antibodies in the SLE patients. In summary, our result indicate that the increased IL-10 production in SLE could be constitutive.     

Investigation of the prevalence and clinical associations of antibodies to human fibronectin in systemic lupus erythematosus.

OBJECTIVES--To assess the prevalence of antibodies to human fibronectin (anti-Fn) in sera of patients with certain connective tissue diseases and to determine their association with disease activity and the pattern of organ involvement in patients with systemic lupus erythematosus (SLE). METHODS--A capture enzyme linked immunosorbent assay (ELISA) was developed to quantify anti-Fn antibodies in serum samples from 65 patients with well characterised SLE, 50 with rheumatoid arthritis (RA), 15 with Behçet's disease (BD), 15 with systemic vasculitis and 36 healthy subjects. An anti-Fn antibody titre greater than mean + 3SD of the healthy control log values after back transformation to the normal scale was considered positive. Disease activity in SLE patients was scored using the British Isles Lupus Assessment Group (BILAG) Index. Erythrocyte sedimentation rate (ESR), concentrations of anti-dsDNA antibody, soluble interleukin-2 receptors (sIL-2R), C3, C4, C3 degradation products (C3dg) and immunoglobulin, and antinuclear antibody (ANA) titres were measured in blood samples from SLE patients; neopterin concentration was measured in corresponding urine samples. RESULTS--Anti-Fn antibodies were found in 22 of 65 SLE patients (33.8%), seven of 50 with RA (14%), one of 15 with BD (6.6%) and none of the 15 subjects with vasculitis. Thirty SLE patients had active disease and 35 had inactive disease; their median anti-Fn concentrations were 117 u/ml (range 47-450) and 68 u/ml (range 17-334), respectively (p = 0.0001). The presence of anti-Fn did not correlate with immunoglobulin concentrations or ANA titres in these sera. No significant difference was found between SLE patients with disease activity in one major organ system compared with multiple organ involvement, as defined by BILAG (p = 0.19). However, patients with musculoskeletal manifestations had consistently greater anti-Fn concentrations compared with patients with other clinical manifestations. There were significant correlations between amounts of anti-Fn in SLE sera and ESR (rs = 0.25, p = 0.045), sIL-2R (rs = 0.28, p = 0.024) and urine neopterin (rs = 0.3, p = 0.016) but not with serum anti-dsDNA antibody titres, plasma C3, C3dg or C4. However multiple regression analysis showed a low significant correlation only with sIL-2R and BILAG score (p = 0.047 and 0.042, respectively). CONCLUSION--Anti-Fn antibodies were detected in 34% of SLE patients and in small proportions of RA and BD patients. An association between serum anti-Fn and disease activity in SLE has been identified and most SLE patients with musculoskeletal involvement had increased anti-Fn antibody concentrations.     

Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.     

Serum levels of IL-10, IL-6, IL-1ra, and sIL-2R in patients with psoriatic arthritis

Our objective was to evaluate the levels of interleukin-6 (IL-6), soluble receptors of IL-2 (sIL-2R), IL-10, and IL-1 receptor antagonists (IL-1ra) in the serum of patients with psoriatic arthritis (PsA) and to assess the correlation between these levels and parameters of clinical activity of skin and joint disease. In total, 34 patients with PsA and ten healthy volunteers participated in the study. Assessment of joint disease included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory spinal back pain, and Schober test. Current severity of skin disease was graded according to the psoriasis area and severity index (PASI). Erythrocyte sedimentation rate (ESR) was determined as a marker of disease activity. Serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were measured by an enzyme immunoassay kit. Significantly higher serum levels of IL-6, sIL-2R, IL-1ra, and IL-10 were found in patients with PsA in comparison with healthy volunteers. A statistically significant correlation was found between levels of sIL-2R and PASI, whereas no association was found with clinical parameters of joint severity. Levels of IL-1ra correlated with the number of tender and swollen joints. No correlation was found between levels of IL-6, IL-10, and clinical parameters of skin and joint severity. In the group of patients with PsA, serum levels of sIL-2R clearly correlated with severity of skin disease, whereas levels of IL-1ra were associated with joint severity. Received: 18 June 1999 / Accepted: 1 October 1999     

The influence of corticosteroids on IL-6/IL-6R system in patients with Graves' ophthalmopathy

IL-6 and its soluble receptor (IL-6R) appeared as reliable markers of inflammation activity in autoimmune diseases. The aim of the study was an estimation of serum IL-6 and sIL-R in patients with Graves' disease with ophthalmopathy during treatment with corticosteroids to assess their potential as a guideline of immunosuppressive therapy. We detected serum HIL-6 and IL-6R in three groups of subjects: 18 patients with clinical symptoms of ophthalmopathy (Clinical Activity Score > or = 3, anamnesis of GO > or = 1 yr), 16 patients with Graves' disease without ophthalmopathy (Gd) and 14 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of soluble IL-6 and IL-6R in the serum were determined by the ELISA method (Quantikine kit, R&D Systems, Minneapolis). The statistical significance was estimated by the Mann-Whitney U-test. IL-6 concentration was significantly increased in patients with GO in comparison to the controls (12.4 +/- 3.7 vs 11.8 +/- 3.2; p < 0.05). After MP treatment in corticosteroid-responsive patients (improvement in CAS < or = 1) serum concentration of sIL-6R decreased significantly in comparison to pretreatment values (32.8 +/- 4.2 vs 28.6 +/- 4.9; p < 0.05). We found a positive correlation between IL-6 concentration and degree of proptosis. CONCLUSIONS: 1. IL-6/IL-6R system plays an important role in the pathogenesis of GO. 2. IL-6R is a potent prognostic factor for efficacy of the immunotherapy but further investigations are needed.     

Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and autoantibodies production

Interleukin-18 (IL-18) and its inducer IL-12 have multiple biological activities that are important in generating Th1 responses and inflammatory tissue damage. We investigated serum concentration of the novel proinflammatory Th1 cytokine; IL-18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I comprised32 patients of systemic lupus erythmatosus (SLE), Group II comprised 36 patients of rheumatoid arthritis (RA). Group III comprised 9 patients (2 patients of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one patient of Scleroderma, and 2 patients of Mixed connective tissue disease). Group IV is a control group consists of 21 sex and age matched healthy subjects and correlated their levels with autoantibody concentration (ANA and ds-DNA), clinical grades and SLE disease activity index (SLEDAI). Serum IL-18, IL-12, ANA and ds-DNA were measured by enzyme immuno sorbent assay. IL-18, IL-12 and ANA were significantly higher in the three studied groups than in the control group (IL-18; P < 0.001 in the three groups, IL-12; P = 0.019, P = 0.002, and P = 0.006, and ANA; P < 0.001, P = 0.002,and P = 0.006, respectively).ds-DNA was significantly higher in SLE patients than in control group (P < 0.001). There were significant positive correlations between; A) levels of IL-18,and both ANA and ds-DNA in SLE patient (r = 0.41,P = 0.001, r = 0.58 and P=0.001 respectively); and B) IL-18 and ANA in both RA and group III patients (r = 0.32, P = 0.005, r = 0.61and P = 0.022 respectively). Also, there were significant positive correlation between the levels of IL-18 and clinical grades of the three groups (r = 0.60,P = 0.001, r = 0.79,P = 0.001, r = 0.78 and P= 0.001 respectively). In SLE patients , IL-18 concentration shows significant positive correlation with SLEDAI score (r = 0.76, P = 0.001). In conclusion, the elevation of proinflammatory cytokines (IL-18 and IL-12 ) may trigger the inflammatory process in immune rheumatic diseases and IL-18 is correlated with disease activity     

Comparison of serum IL-1β, sIL-2R,IL-6, and TNF-α levels with disease activity parameters in ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic, inflammatory, rheumatological disease affecting primarily the sacroiliac joint and vertebral column, with an etiology that remains obscure. Cytokines are soluble proteins that have specific roles in inflammatory response, arranging the interaction between cells of the immune system both in natural and specific immune reactions. This study was planned to evaluate the relation between the level of cytokines and the clinical and laboratory findings of patients with AS compared to healthy subjects. In this study, we demonstrated increased serum levels of soluble interleukin-2 receptor (sIL-2R), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in patients with AS compared with healthy subjects. Only IL-1β levels were not increased in AS patients. We found a correlation between C-reactive protein and IL-6 levels and between erythrocyte sedimentation rate and sIL-2R, IL-6 and TNF-α levels. Only the sIL-2R level was correlated with Bath AS Metrology Index and Bath AS Functional Index. We suggest that sIL-2R, IL-6, and TNF-α may have a role in the pathogenesis of AS and that their serum levels can be used as disease activity parameters and tools for diagnosis.     

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

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