Serum Levels Of Soluble Interleukin Research Articles

Serum levels of soluble interleukin 2 receptor (sIL-2R), tumor necrosis factor-alpha (TNF-α), and immunoglobulin M are correlated with the disease extent in childhood Langerhans cell histiocytosis.

This study aimed to identify peripheral parameters associated with the severity of Langerhans cell histiocytosis (LCH) and to look for indicators associated with improvement in LCH patients with risk-organ involvement. This study enrolled LCH patients who were assessed as active disease-better (AD-B) after treatment. Patients were divided into the single system (SS) group, multisystem disease without risk-organ involvement (RO- MS) group, and multisystem disease with risk-organ involvement (RO + MS) group. Serum cytokines, immunoglobulins, and lymphocyte subsets were measured at admission for all three groups. Changes in these indicators after treatment were also analyzed. From January 2015 to January 2022, a total of 46 patients were recruited in the present study, including 19 patients (41.3%) in the SS group, 16 patients (34.8%) in the RO- MS group, and 11 patients (23.9%) in the RO + MS group. Serum levels of soluble interleukin 2 receptor (sIL-2R) (> 912.5 U/mL), tumor necrosis factor-alpha (TNF-α) (> 20.3pg/mL), and immunoglobulin M (< 1.12g/L) were found to be effective in identifying patients in the RO + MS group. Furthermore, the levels of sIL-2R (SS vs RO + MS: P = 0.002, RO- MS vs RO + MS: P = 0.018) and CD8 + T-cell count (SS vs RO + MS: P = 0.028) significantly declined in the RO + MS group after treatment, indicating disease improvement. The levels of sIL-2R and TNF-α were positively correlated with the extent of disease, while the levels of IgM were negatively correlated with the extent of disease. Additionally, the levels of sIL-2R and CD8 + T-cell count could serve as useful indicators to evaluate the treatment response in RO + MS-LCH patients.

Diagnostic Rate of Malignant Lymphoma Using Soluble Interleukin 2 Receptor Levels in Patients with Cervical Lymphadenopathy

Abstract Background and Objectives Cervical lymph node enlargement is observed in various diseases, including malignant lymphoma (ML). Open biopsy of the enlarged lymph node is frequently required for diagnosis, especially when ML is suspected. Serum levels of soluble interleukin 2 receptor (sIL-2R) may be useful as a biomarker of ML. This study aimed to determine whether the measurement of serum sIL-2R levels might be useful to diagnose ML. Materials and Methods We retrospectively reviewed the data of 281 patients who had undergone open cervical lymph node biopsy at our institution between 2015 and 2019, including 157 males and 124 females (age range, 5–90 years). Data on the patients' age, final diagnosis, and serum sIL-2R levels were obtained from their medical records. Results Overall, 184 cases of MLs and 97 cases of other diseases (non-MLs [NMLs]) were recorded. The mean age was significantly higher and mean serum sIL-2R levels were significantly higher in the ML group than in the NML group. In the ML group, the serum sIL-2R levels were significantly higher in patients with T cell lymphoma than in those with B cell lymphoma. The area under the receiver operating characteristic curve of the serum sIL-2R level for predicting ML was 0.711, and a serum sIL-2R level of 1,246 U/mL was associated with the maximum value of the sensitivity + specificity for the diagnosis of ML. Multivariate analysis revealed that the area under the receiver operating characteristic curve increased to 0.758 for patients aged &gt;61 years and patients with serum sIL-2R levels of &gt;1,246 U/mL. Conclusions Among patients presenting with cervical lymphadenopathy, the measurement of serum sIL-2R levels could be useful for distinguishing between patients with and without ML, with a cutoff level of 1,246 U/mL for the diagnosis of ML.

Proinflammatory TH17 cytokine activation, disease severity and outcomes in peripartum cardiomyopathy

BackgroundImmune dysregulation is implicated in the development and clinical outcomes of peripartum cardiomyopathy (PPCM). Methods and results98 women with PPCM were enrolled and followed for 1 year postpartum (PP). LVEF was assessed at entry, 6-, and 12-months PP by echocardiography. Serum levels of soluble interleukin (IL)-2 receptor (sIL2R), IL-2, IL-4, IL-17, IL-22, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by ELISA at entry. Cytokine levels were compared between women with PPCM by NYHA class. Outcomes including myocardial recovery and event-free survival were compared by cytokine tertiles. For cytokines found to impact survival outcomes, parameters indicative of disease severity including baseline LVEF, medications, and use of inotropic and mechanical support were analyzed. Levels of proinflammatory cytokines including IL-17, IL-22, and sIL2R, were elevated in higher NYHA classes at baseline. Subjects with higher IL-22 levels were more likely to require inotropic or mechanical support. Higher levels of TNF-α and IL-22 were associated with poorer event-free survival. Higher TNF-α levels were associated with lower mean LVEF at entry and 12 months. In contrast, higher levels of immune-regulatory cytokines such as IL-4 and IL-2 were associated with higher LVEF during follow up. ConclusionProinflammatory cytokines IL-22 and TNF-α were associated with adverse event-free survival. IL-17 and IL-22 were associated with more severe disease. In contrast, higher levels of IL-2 and IL-4 corresponded with higher subsequent LVEF. Increased production of TH17 type cytokines in PPCM correlated with worse disease and outcomes, while an increased immune-regulatory response seems to be protective.

Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes.

ObjectivesIdiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids.MethodsThis prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed.ResultsA total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14).ConclusionsPatients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids.

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease

We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.

Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment-resistant major depressive disorder.

AimA substantial proportion of major depressive disorder patients are treatment‐resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment‐resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment‐resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment‐resistant major depressive disorder.MethodGiven that immune‐inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine‐related molecules could serve as clinically useful biomarkers of treatment‐resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor‐α, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy.ResultsThe serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor‐α, was significantly higher in treatment‐resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment‐resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin‐6 receptor level measurement was useful for identification of treatment‐resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology‐Self Report score (QIDS‐SR16) as a target variable showed that only serum soluble interleukin‐6 receptor level could explain the severity of major depressive disorder.ConclusionBased on these results, we recommend measurement of serum soluble interleukin‐6 receptor level to discriminate treatment‐resistant major depressive disorder patients. High serum soluble interleukin‐6 receptor level is associated with the pathogenesis of treatment‐resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans‐signaling system in onset of treatment‐resistant major depressive disorder.

Prognostic nomogram incorporating inflammatory cytokines for overall survival in patients with aggressive non-Hodgkin's lymphoma.

BackgroundThis study aimed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin's lymphoma.MethodsA total of 228 patients with diffuse large B-cell lymphoma (DLBCL) received R-CHOP-based regimens from a prospective randomized study (NCT01852435) were included as a training cohort. Other cohorts of 886 lymphoma patients were served as validation cohorts. Lymphocyte-monocyte ratio (LMR), serum levels of soluble interleukin s(IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α), were assessed before treatment. Least absolute shrinkage and selection operator (LASSO) regression were used to select variables for nomogram of overall survival (OS). The predictive accuracy of the nomogram was determined by concordance index (C-index).FindingsThe nomogram included lactate dehydrogenase (LDH), sIL-2R, TNF-α and decreased LMR. The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL, PTCL, NKTCL and ASCT, which were superior to the predictive power of International Prognostic Index (IPI, 0.67 to 0.84) or NCCN-IPI (0.59 to 0.78), but not in those of indolent lymphoma like FL and MALT.InterpretationsThe nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin's lymphomas.FundNational Natural Science Foundation of China, the Shanghai Commission of Science and Technology, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of SHDC, and Chang Jiang Scholars Program.

Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder.

To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.

Serum soluble interleukin 2 receptor (sIL‐2R) as a marker of acute rejection in renal transplant children

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.

Sarcoidosis does not belong to or overlap with immunoglobulin G4–related diseases based on an assessment of serum immunoglobulin G4 levels in cardiac and noncardiac sarcoidosis

Although sarcoidosis may exhibit histopathologic features similar to those of a newly emerging clinical entity, immunoglobulin G4-related sclerosing disease, sarcoidosis is currently not considered to be associated with immunoglobulin G4-related immunoinflammation. Not many studies on this association have been reported. We investigated serum immunoglobulin G4 levels among patients with sarcoidosis with or without cardiac involvement (cardiac sarcoidosis and non-cardiac sarcoidosis patients). The mean serum immunoglobulin G4 level among the 65 patients with sarcoidosis was 56.8 ± 43.0 mg/dL, which did not significantly differ between patients with cardiac sarcoidosis (54 ± 48 mg/dL, n = 12) and patients without cardiac sarcoidosis (58 ± 42 mg/dL; n = 53). Serum level of soluble interleukin 2 receptor, a potent marker that may reflect sarcoidosis activity, was elevated in cardiac sarcoidosis (910 ± 683 U/L) and noncardiac sarcoidosis (689 ± 399 U/L) but did not significantly differ between the groups. Immunohistochemistry of cardiac or lymph node specimens from patients with cardiac sarcoidosis showed only sparse or no infiltration of immunoglobulin G4-positive lymphocytes, in contrast to the moderate to severe infiltration of CD68-positive macrophages and CD45-positive lymphocytes. Although the number of study subjects was small, these findings collectively suggest that regardless of the presence or absence of cardiac involvement, sarcoidosis does not belong to or overlap with immunoglobulin G4-related sclerosing disease.

Serum Levels of Soluble Interleukin 10 (IL-10) in Patients with Hodgkin's Lymphoma: Predictive Value in Advanced Stage.

Introduction. Hodgkin's lymphoma has a high rate of cure with current therapies; however, some patients do not respond or relapse after therapy. The aim of this study is to assess the predictive value of serum soluble Interleukin 10 (sIL-10) at diagnosis in these patients.Patients and Methods. Two cohorts of 80 consecutive patients with Hodgkin's lymphoma (40 male and 40 female) diagnosed and treated in the same institution were evaluated. All of them were clinically staged according to Ann Arbor system. The following parameters were evaluate for prognosis: age, sex, histology, clinical symptoms, extra-nodal disease, stage, treatment, blood counts (hemoglobin, white blood cells, lymphocyte and platelets), blood chemistry (b-2-microglobulin, tymidine-kinase and LDH levels), serum soluble IL-10 and IL-6 levels by using an ELISA method.Statistics: Continuous variables were compared by using Wilcoxon signed-rank test, contingence tables were used for dichotomized variables; the optimal cut-off values were calculated by using CART method. Survival curves were estimated by Kaplan-Meier method and mantel-Cox were used to compare them. Cox multiple regression analysis was performed to determinate the independent contribution of the variables.Patients received COPP (n=16), hybrid schedule (n=21), ABVD (n=35), radiotherapy alone (n=6), surgery alone (n=1), and Stanford V (n=1) as first-line therapy.Results. Median patient age was 36 years (range: 15–85 years), predominant histology was nodular-sclerosis (70%), 27 patients (34%) presented B symptoms. Bulky disease was present in 14 (17%) and bone marrow involvement in 6%. Thirty-six patients were considered as having advanced stage (II-B or II + bulky disease. III-B or III + bulky disease, and IV). The overall response rate was 92% (85% CR/CRu, and 7% PR). Eleven out of 68 patients who achieved a CR/CRu relapsed. Serum IL-10 levels were significant higher in patients with B symptoms and extra-nodal disease and correlated with β-2-microglobulin, tymidine-kinase, and (inversely) hemoglobin levels. The optimal sIL-10 serum level cut-off was established in 13.8 pg/mL. %: 54 out of 57 patients (95%), and 14 out of 23 of patients below and above this level respectively achieved a CR/CRu (P<0.001).With a median follow-up of 86 months the OS and EFS are 77% and 69% respectively. Only sIL-10 > 13.8 pg/mL had independent predictive value for EFS in the multivariate analysis.Based on this study and combining stage a serum levels of sIL-10, three subgroups could have been identify:Patients with early disease: 85% EFS at 5 years;patients with advanced stage (according to the above mentioned definition ) and serum levels of sIL-10 less than 13.8 pg/mL: 72% EFS at 5 years.; andpatients with advanced stage and serum levels of sIL-10 superior to 13.8 pg/mL: 29% EFS at 5 years (P=0.0001).Conclusion. Serum levels of sIL-10 can help us to identify a subgroup of patients with advanced disease and poorer response and EFS who may benefit from more aggressive first-line therapy. [Display omitted]

Subcutaneous panniculitis-like T-cell lymphoma presenting with hemophagocytic lymphohistiocytosis and skin lesions with characteristic high-resolution ultrasonographic findings

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual type of skin lymphoma, characterized by subcutaneous soft tissue infiltration with pleomorphic T-cells and benign macrophages that mimic panniculitis. Hemophagocytic lymphohistiocytosis is a rare but potentially fatal disorder which is thought to result from uncontrolled activation and proliferation of T-cells and excessive activation of macrophages. Hemophagocytic lymphohistiocytosis have been reported as the presenting feature in 37% of SPTCL patients. High-resolution ultrasonographic appearance of SPTCL with a characteristic finding has been described in only one patient. We report a 28-year-old woman with hemophagocytic lymphohistiocytosis presented with nonremitting fever, thrombocytopenia, hypofibrinogenemia, hyperferritinemia, increased serum levels of soluble interleukin (IL)-2 receptors and hemophagocytosis in bone marrow examination. Markedly elevated level of serum IL-18 was also demonstrated in our patient. The fever subsided and the ferritin level declined to normal after treatment with oral steroid and etoposide. No evidence of hemophagocytosis was revealed in a follow-up bone marrow examination. However, nonremitting high fever and panniculitis-like skin lesions over her back, arm, lower abdominal wall, and bilateral pretibial regions developed 1 month later. A high-resolution ultrasonography revealed thickening of the subcutaneous fat layer with homogeneous hyperechogenicity pattern and poor-defined margin over the skin lesions. An ultrasound-guided excision biopsy of the nodular lesion over left upper arm was performed and the histopathology showed neoplastic cells with hyperchromatic nucleoli, which extended from deep dermis to subcutaneous fat. The immunochemical stain showed a T-cell lineage of tumor cells. SPTCL was diagnosed and the skin lesions subsided gradually after treatment with anthracycline-based combination chemotherapy.

Clinical significance of intracytoplasmic nm23-H1 expression in diffuse large B-cell lymphoma.

Recently, we established an ELISA technique for measuring nm23-H1 protein in serum and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DLBCL). By analyzing a consecutive series of 172 untreated DLBCL patients, we found that 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with performance status 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of soluble interleukin 2 receptor, and elevated serum level of C-reactive protein. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen between patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. We suggest that nm23-H1 expression is a prognostic factor for DLBCL, and that it is as important as serum nm23-H1, both of which are useful for planning a treatment strategy.

Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. Are there any useful markers for predicting outcome after Helicobacter pylori eradication?

Although Helicobacter pylori eradication is effective in treating low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the condition in some patients deteriorates even after the eradication. Therefore, it is important to predict the disease outcome before starting H. pylori eradication. We investigated the usefulness of flow cytometry, quantifying CD19- and CD20-positive B lymphocytes in MALT lymphoma tissue, for predicting the disease outcome after H. pylori eradication. Tissue specimens from 14 patients with H. pylori-positive low-grade gastric MALT lymphoma were examined by histology, Southern blotting, and flow cytometry before therapy. Serum levels of soluble interleukin (IL)-2 receptor were also measured. The relationship between the data and the prognosis after H. pylori eradication was analyzed. Remission occurred in 10 of the 14 patients. The condition in the 4 remaining patients deteriorated even after H. pylori eradication. The percentages of CD19- and CD20-positive cells in MALT lymphoma tissue from the patients in remission were both significantly lower than those in the tissue from patients not in remission. Indeed, 4 of the 5 patients in whom both CD19- and CD20-positive cells accounted for more than 50% of the total number of lymphocytes had gastrectomy, whereas all patients in whom both CD19- and CD20-positive cells accounted for less than 50% of the total number of lymphocytes achieved remission. Although immunoglobulin gene rearrangement was present in all patients operated on, there were also 6 patients whose MALT lymphoma was ameliorated in spite of the presence of gene rearrangement. The serum level of soluble IL-2 receptor was in the normal range in all patients tested. Analysis of mature B-cell markers in MALT lymphoma tissue is more useful than the examination of immunoglobulin gene rearrangement or serum levels of soluble IL-2 receptor in predicting the outcome of low-grade gastric MALT lymphoma after H. pylori eradication.

Modulation of coronary vasomotor tone by cytokines in cardiac transplant recipients.

Upon exposure to cytokines, endothelial cells may undergo profound alterations of vasomotor function. In this study, we characterized the relationship between coronary epicardial and microvascular vasomotor function and expression of specific cytokine patterns in human heart transplant recipients. We studied 49 cardiac transplant recipients, without acute rejection or infection at an average of 6+/-3 months after transplantation. Coronary resistance vessel function was measured in an endothelium-dependent manner with acetylcholine (5 and 150 microg/5 min; intracoronary injection) and in an endothelium-independent manner with adenosine (400 and 800 microg/5 min; intracoronary injection) using an intracoronary Doppler flow wire. Simultaneous epicardial diameter changes were measured using quantitative coronary angiography. Coronary sinus and aortic serum levels of soluble interleukin (IL)-2 receptor and soluble tumor necrosis factor-a receptors (sTNF-R1 and sTNF-R2), TNF-alpha, and IL-6 were determined. Transcardiac cytokine release (coronary sinus minus aortic levels) was correlated with coronary vasomotor function. The highest amounts of cardiac cytokine release were observed for IL-6 (32+/-14% increase) and sTNF-R1 (26+/-13% increase). A significant inverse correlation between microvascular endothelial function and cardiac release of soluble IL-2 receptor (P=0.04) and IL-6 (P=0.03) was detected, whereas a positive correlation was observed to sTNF-R1 (P=0.004). Distal epicardial endothelial vasomotion was inversely correlated to transcardiac sTNF-R2 release (P=0.03). Cytokine production and activation, a common phenomenon early after heart transplantation, is related at least in part to endothelial vasomotor dysfunction of the epicardial and microvascular compartment. These results support the hypothesis that coronary endothelial dysfunction after cardiac transplantation is an immunologic phenomenon. Since endothelial dysfunction seems to be a crucial step in the pathogenesis of cardiac allograft vasculopathy, coronary cytokine suppression should be a therapeutic target of improved future immunosuppressive regimens.

Psoriasis: comparison of immunological markers in patients with acute and remission phase

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), β2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54 + lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and β2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.

Cell-mediated immunity in patients with head-neck carcinoma

The immune system involvement in psoriasis has been documented by the presence of activated T-cells both in peripheral blood and in psoriatic skin lesions and by the intervention of cytokines in the inflammatory process. On this basis, we have undertaken a study in order to examine, in addition to activation markers such as CD25 and CD54 (ICAM-1) on peripheral blood mononuclear cells (PBMNCs) surface, serum levels of soluble interleukin (IL)-2 receptor (sIL-2R), soluble ICAM-1 (sICAM-1), soluble CD4 (sCD4), soluble CD8 (sCD8), β2-microglobulin and fibronectin (FN) in psoriatic patients analyzed both in acute and remission phase obtained by topical therapy alone. Our results show that PBMNCs expressing IL-2 receptor (CD25) were increased both in percentage and absolute number in respect to controls, and were not modified after remission. On the contrary, the significantly higher number of CD54+ lymphocytes evaluated in acute psoriasis, showed a reduction during the remission phase, even if the values persisted higher than controls. Serum levels of sIL-2R, sICAM-1, sCD4, sCD8 and β2-microglobulin were significantly higher than controls both in acute and remission phase; only FN levels were found to be lower, in patients evaluated both in acute psoriasis and after therapy, in respect to normal donors. On the whole, these results seem to indicate the persistence of both cellular and soluble activation markers even in psoriasis remission phase; in this light, we can suppose that topical therapy alone is not able to efficiently down-regulate activation mechanisms involved in the pathogenesis of the disease.

Prediction of sustained response to interferon alpha therapy with serum soluble interleukin 2 receptor levels in patients with chronic hepatitis C

It is difficult to predict sustained response to interferon alpha therapy for patients with chronic hepatitis C. Loss of serum hepatitis C viral RNA (HCV-RNA) and normal serum alanine aminotransferase (ALT) level at the end of treatment do not necessarily mean sustained response. Relapses are very common. In this study, serum levels of soluble interleukin 2 receptor (sIL-2R, an indicator of immune response) were investigated to see if they are helpful to predict sustained response. We studied consecutive twenty patients with chronic hepatitis C who had HCV-RNA negativity and normal ALT levels at the end of interferon alpha therapy. Total doses of interferon ranged from 288 million units (MU) to 480MU. Serum HCV-RNA sequences were examined before and at the end of treatment by nested polymerase chain reaction (PCR) using primers to the 5′ noncoding region. Serum sIL-2R levels were also measured before and at the end of treatment using enzyme-linked immunoassay. Eight of twenty (40%) patients were sustained responders and the rest of the patients (60%) relapsed (partial responders). Serum sIL-2R levels in sustained responders decreased (−96.2 ± 45.2 IU/l), whereas partial responders showed increase in serum sIL-2R levels (81.3 ± 50.5 IU/l). The difference in sIL-2R changes between sustained responders and partial responders was significant ( P < 0.01). In particular, six of six (100%) patients who showed more than 50 IU/l increase in sIL-2R levels were partial responders. In conclusion, monitoring serum sIL-2R levels with HCV-RNA and ALT is useful to predict sustained response to interferon.

Granulocyte-colony-stimulating factor induces increased serum levels of soluble interleukin 2 receptors preceding engraftment in autologous bone marrow transplantation.

The serum levels of soluble interleukin 2 receptors (sIL-2R) were determined in 19 patients who received high-dose chemotherapy and an autologous or syngeneic bone marrow transplant (BMT) for treatment of Hodgkin's disease (n = 18) or non-Hodgkin's lymphoma (n = 1). Twelve patients received granulocyte colony-stimulating factor (G-CSF) from day 0 or day +1 after autologous BMT until the white blood cell count had been stable for 9 d above 1 x 10(9)/l, the remaining seven patients did not receive growth factors. In all G-CSF-treated patients the sIL-2R levels increased steadily in the early post-transplant course, even in the absence of infection. This increase was statistically significant 2-4 d prior to the appearance of leucocytes in the peripheral blood (median 340 pM versus median 256 pM immediately after BMT, P < 0.025) and peaked with the appearance of first peripheral blood leucocytes (median 536 pM, P < 0.001). Cessation of G-CSF administration resulted in a decline of sIL-2R levels. In contrast, five of seven patients without G-CSF treatment did not exhibit an sIL-2R increase before or at the time of engraftment. Infection was associated with a rise of sIL-2R levels. A correlation between sIL-2R levels and total leucocyte count, lymphocyte count, or CD25+ lymphocyte count was not evident. These data suggest that after autologous BMT G-CSF induces increased sIL-2R levels, which occur independent of lymphocyte activation. This may be compatible with involvement of immature bone marrow cells in G-CSF-induced sIL-2R release.

Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease

Serum levels of soluble interleukin 2 receptor (sIL-2R) have been proposed as a clinical marker of inflammatory bowel disease. The source of sIL-2R in patients with Crohn's disease and ulcerative colitis is unknown, and other soluble receptors have not been investigated. In the present study, sIL-2R and soluble CD8 and CD4 levels were measured in plasma and culture supernatants of peripheral blood and intestinal mucosal mononuclear cells from patients with inflammatory bowel disease, surgical controls, and healthy subjects. Level of plasma sIL-2R was significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy volunteers. Intestinal cells always produced more sIL-2R than peripheral cells. Spontaneous sIL-2R production by mucosal cells was significantly elevated in Crohn's disease but not in ulcerative colitis supernatants compared with levels of surgical controls. Soluble CD8 and CD4 were poor indicators of systemic or mucosal immunity. A positive correlation was found between plasma sIL-2R and spontaneous production by intestinal cells of patients with Crohn's disease and surgical control patients, whereas ulcerative colitis plasma sIL-2R correlated with spontaneous production by peripheral cells. The association of plasma or spontaneous sIL-2R levels with the degree of intestinal inflammation was weak, and there was a wide overlap with control values. Therefore, caution should be used before considering sIL-2R an accurate marker of inflammatory bowel disease activity.