Soluble IL-2 Receptor Concentrations Research Articles

Kappa Free Light Chains, Soluble Interleukin-2 Receptor, and Interleukin-6 Help Explore Patients Presenting With Brain White Matter Hyperintensities.

IntroductionMany patients are referred to multiple sclerosis (MS) tertiary centers to manage brain white matter hyperintensities (WMH). Multiple diagnoses can match in such situations, and we lack proper tools to diagnose complex cases.ObjectiveThis study aimed to prospectively analyze and correlate with the final diagnosis, cerebrospinal fluid (CSF) interleukin (IL)-1β, soluble IL-2 receptor (CD25), IL-6, IL-10, and kappa free light chains (KFLC) concentrations in patients presenting with brain WMH.MethodsAll patients over 18 years addressed to our MS tertiary center for the diagnostic workup of brain WMH were included from June 1, 2020, to June 1, 2021. Patients were separated into three groups—MS and related disorder (MSARD), other inflammatory neurological disorder (OIND), and non-inflammatory neurological disorder (NIND) groups—according to clinical presentation, MRI characteristics, and biological workup.ResultsA total of 176 patients (129 women, mean age 45.8 ± 14.7 years) were included. The diagnosis was MSARD (n = 88), OIND (n = 35), and NIND (n = 53). Median CSF KFLC index and KFLC intrathecal fraction (IF) were higher in MSARD than in the OIND and NIND groups; p < 0.001 for all comparisons. CSF CD25 and IL-6 concentrations were higher in the OIND group than in both the MSARD and NIND groups; p < 0.001 for all comparisons. KFLC index could rule in MSARD when compared to NIND (sensitivity, 0.76; specificity, 0.91) or OIND (sensitivity, 0.73; specificity, 0.76). These results were similar to those with oligoclonal bands (sensitivity, 0.59; specificity, 0.98 compared to NIND; sensitivity, 0.59; specificity, 0.88 compared to OIND). In contrast, elevated CSF CD25 and IL-6 could rule out MSARD when compared to OIND (sensitivity, 0.58 and 0.88; specificity, 0.95 and 0.74, respectively).DiscussionOur results show that, as OCBs, KFLC biomarkers are helpful tools to rule in MSARD, whereas elevated CSF CD25 and IL-6 rule out MSARD. Interestingly, CSF IL-6 concentration could help identify neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and central nervous system (CNS) vasculitis. These results need to be confirmed within more extensive and multicentric studies. Still, they sustain that KFLC, CSF CD25, and CSF IL-6 could be reliable biomarkers in brain WMH diagnostic workup for differentiating MSARD from other brain inflammatory MS mimickers.

Autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluids are useful for the diagnosis of central nervous system invasion caused by haematological malignancies.

Invasion of the central nervous system by haematological malignancies is diagnosed by cytological analyses of cerebrospinal fluid or diagnostic imaging, while quantitative biomarkers for central nervous system invasion are not available and needed to be developed. In this study, we measured the concentrations of autotaxin and soluble IL-2 receptor in cerebrospinal fluid and evaluated their usefulness as biomarkers for central nervous system invasion. We observed that both the autotaxin and soluble IL-2 receptor concentrations in cerebrospinal fluid were higher in subjects with central nervous system invasion than in those without, and the cerebrospinal fluid concentrations were independent from the serum concentrations of these biomarkers. ROC analyses revealed that the soluble IL-2 receptor concentration in cerebrospinal fluid was a strong discriminator of central nervous system invasion in subjects with haematological malignancies, while the autotaxin concentration in cerebrospinal fluid also had a strong ability to discriminate central nervous system invasion when the subjects were limited to those with lymphoma. The combined measurement of autotaxin and soluble IL-2 receptor in cerebrospinal fluid improved the sensitivity without notably reducing the specificity for central nervous system invasion in subjects with lymphoma when central nervous system invasion was diagnosed in cases where either value was beyond the respective cut-off value. These results suggest the possible usefulness of soluble IL-2 receptor and autotaxin concentrations in cerebrospinal fluid for the diagnosis of central nervous system invasion.

Analysis of serum markers of cellular immune activation in patients with bullous pemphigoid.

Experimental models of bullous pemphigoid (BP), the most frequent subepidermal autoimmune bullous disease, revealed that the immune response leading to blister formation represents an incompletely understood complex process involving different inflammatory cells. In contrast to previous reports commonly focusing on limited molecular and cellular phenotypes of the disease, the aim of this study was to investigate a broad spectrum of markers of cellular immune activation in patients with BP. We found that serum levels of soluble CD4, myeloperoxidase, S100A12, eosinophil cationic protein and soluble P-selectin were significantly elevated in patients with active BP compared with normal controls. Mast cell tryptase and neopterin serum levels significantly decreased at the time of clinical remission of the patients. Additionally, serum concentrations of soluble IL-2 receptor, mast cell tryptase and soluble P-selectin were significantly associated with levels of circulating anti-BP180 autoantibodies. Our findings confirm and extend previous reports suggesting some concomitant involvement of a panel of molecules representative for a wide spectrum of cellular players (T cells, mast cells, neutrophils, eosinophils, macrophages and platelets) orchestrating the inflammatory reaction in BP. These data may favour the employment of broad-spectrum or combined immunosuppressants, potentially together with an anticoagulant treatment, over cell- or molecule-specific targeted therapy in patients with this disorder.

The serum concentration of soluble interleukin-2 receptor in patients with Kawasaki disease.

Kawasaki disease is a febrile disease of childhood that is associated with increased inflammatory cytokines and immunoregulatory abnormalities. While the serum concentrations of soluble IL-2 receptor can change under such pathologies, the relevance of the soluble IL-2 receptor concentration in patients with Kawasaki disease has not been specified. We aimed to summarize the existing studies that reported the soluble IL-2 receptor concentrations in patients with Kawasaki disease. Original articles that were published up to July 2016 were collected using a PubMed/Medline-based search engine. A total of nine articles that reported the serum soluble IL-2 receptor concentrations in acute-phase Kawasaki disease were eligible. All of the articles described a high soluble IL-2 receptor concentration in patients with Kawasaki disease relative to the level of controls or the reference range. Two of five articles on patients with coronary artery aneurysms described a significantly higher soluble IL-2 receptor concentration in patients with coronary artery aneurysms than patients without. Two articles on patients with intravenous immunoglobulin therapy described a significant decrease of the soluble IL-2 receptor concentration after the therapy. Accordingly, the serum soluble IL-2 receptor can be a potent marker of disease activity and therapeutic effects in patients with Kawasaki disease; further studies are thus warranted for its use in the clinical setting.

Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients

Aims/hypothesisType 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells.MethodsWe used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples.ResultsWe identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p = 1.17 × 10−3). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p = 4.8 × 10−3).Conclusions/interpretationThe 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-013-3113-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

M-Protein Is Associated With Aggressive Disease In Patients With MALT Lymphoma

IntroductionExtranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) has an indolent clinical course, with overall patient survival at 5 years after diagnosis of more than 85%. Although the cause of death in a significant proportion of MALT lymphoma patients is not the lymphoma itself, some patients experience early relapse or refractory disease. However, the risk factors capable of predicting aggressive disease in MALT lymphoma have not been clearly defined. Patients and MethodsThis is a retrospective pooled analysis of pathologically confirmed extranodal MALT lymphoma patients treated at our institute. Patients with nodal or splenic marginal zone lymphoma were excluded. The primary endpoint was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. ResultsFrom January 2000 to June 2013, 52 extranodal MALT lymphoma patients (26 females and 26 males) were referred to our institution. The median age of the patients was 68 years (range, 43–89 years). Thirty-three (63%) patients had limited stage disease (stage I/II) and 48 (92%) patients had an ECOG performance status of less than 2. The cumulative numbers of patients who were diagnosed with orbit, thyroid, salivary gland, stomach, lung, and intestine disease were 7 (13%), 5 (10%), 9 (17%), 16 (31%), 16 (31%), and 4 (8%), respectively. Fifteen (29%) patients had a prior history of autoimmune disease, and a serum electrophoresis study detected M-protein in 9 (17%) patients (5 patients had IgG, 3 patients had IgM, and 1 patient had IgA). There was no significant correlation between the presence of M-protein and prior history of autoimmune disease (Fisher's exact test, p=0.46). Of the 32 patients who underwent cytogenetic studies, 9 (28%) had cytogenetic aberrations involving MALT1. Histological transformation to diffuse large B-cell lymphoma (DLBCL) was confirmed in 3 patients. After a median follow-up time of 53 months (range, 1–142 months), 16 patients had relapsed (MALT lymphoma relapse or transformation to DLBCL), and 1 patient had died due to lymphoma. The 4-year PFS and overall survival rate were 76.3% (95% confidence interval (CI), 60.0–86.7%) and 98.0% (95% CI, 86.6–99.7%), respectively. Among the clinical variables measured at diagnosis, univariate analysis found that advanced stage, three or more extranodal sites, serum soluble IL-2 receptor concentration higher than 700 IU/L, lymphocyte count higher than 1x10^9/l, hemoglobin concentration lower than 12.5 g/dl, and the presence of M-protein adversely affected PFS (p<0.05). In multivariate analysis including these six variables, only the presence of M-protein remained as a poor prognostic factor for PFS (hazard ratio (HR), 14.5; 95% CI, 1.47–142; p=0.021). The 4-year unadjusted PFS for patients with M-protein was 14.8% (95% CI, 7.36–47.6%), which was significantly poorer than that of patients without M-protein (90.9% [95% CI, 74.0–97.0%]; HR, 11.9; 95% CI, 3.46–41.1; log-rank, p<0.001). Seven of the 9 patients who had M-protein received rituximab-containing combination chemotherapy (R-CHOP 5 and R-CVP 2), and 5 patients relapsed in a relatively short time (median, 10 months; range, 2–54 months). ConclusionExtranodal MALT lymphoma patients with M-protein had an increased risk of early disease progression. Patients with M-protein were more likely to had advanced stage disease (p=0.005) and more than three extranodal sites (p=0.02) compared to patients without M-protein. However, multivariate analysis showed that the prognostic impact of M-protein was better than that of advanced stage disease and the number of extranodal sites. Further studies are required to determine differences between the biological backgrounds of patients with and without M-protein, and a novel treatment strategy to obtain a durable disease control.▪ Disclosures:No relevant conflicts of interest to declare.

Utility of Serum Neopterin and Serum IL-2 Receptor Levels to Predict Absolute CD4 T Lymphocyte Count in HIV Infected Cases

A prospective study was carried out to evaluate the efficacy of serum neopterin and soluble IL-2 receptor (sIL-2R) concentrations in comparison to CD4 count to study the progression of HIV disease and monitor response to ART in HIV cases. One hundred newly diagnosed HIV seropositive subjects were recruited. CD4 counts were determined by FACS system. Serum neopterin and sIL-2R levels were measured using enzyme immunoassay. In our study, levels of neopterin and sIL-2R were significantly higher in subjects with CD4 <200 cells/μL (with S. neopterin levels of >25.1 nmol/L and sIL-2R levels of >47.1 pM as cutoff values for CD4 <200 cells/μL) compared to those in subjects with CD4 >200 cells/μL at baseline which indicate that these markers can be utilized for initiation of ART in HIV cases. The levels of these markers decreased significantly after initiation of ART. In patients with CD4 >200 cells/μL, these markers are helpful in predicting disease progression.

Hepatitis E Virus Quasispecies and the Outcome of Acute Hepatitis E in Solid-Organ Transplant Patients

Hepatitis E virus (HEV) infections are responsible for chronic hepatitis in immunocompromised patients, and this can evolve to cirrhosis. Like all RNA viruses, HEV exists as a mixture of heterogeneous viruses defining quasispecies. The relationship between the genetic heterogeneity described as a quasispecies, cytokine secretion, and the outcome of acute hepatitis in immunocompromised patients remains to be elucidated. We cloned and sequenced the region encoding the M and P capsid domains of HEV from eight solid-organ transplant (SOT) patients with acute HEV infection who subsequently cleared the virus and from eight SOT patients whose infection became chronic. We analyzed the cytokines and chemokines in the sera of these SOT patients by multianalyte profiling. The nucleotide sequence entropy and genetic distances were greater in patients whose infections became chronic. A lower K(a)/K(s) ratio was associated with the persistence of HEV. The patients who developed chronic infection had lower serum concentrations of interleukin-1 (IL-1) receptor antagonist and soluble IL-2 receptor. Increased concentrations of the chemokines implicated in leukocyte recruitment to the liver were associated with persistent infection. Those patients with chronic HEV infection and progressing liver fibrosis had less quasispecies diversification during the first year than patients without liver fibrosis progression. Great quasispecies heterogeneity, a weak inflammatory response, and high serum concentrations of the chemokines involved in leukocyte recruitment to the liver in the acute phase were associated with persistent HEV infection. Slow quasispecies diversification during the first year was associated with rapidly developing liver fibrosis.

Effects of Sleep Deprivation on Nocturnal Cytokine Concentrations in Depressed Patients and Healthy Control Subjects

Previous studies have reported alterations of cytokine and cytokine-receptor concentrations in psychiatric patient populations, including patients with major depressive disorder (MDD). However, study results are conflicting, and possible causes for these abnormalities are unknown. Since sleep deprivation may induce a rapid improvement of mood in depressed patients, the authors investigated the impact of total sleep deprivation (TSD) for one night, and subsequent recovery sleep, on nocturnal concentrations of interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1RA), and soluble IL-2 receptor (sIL-2R) in 15 unmedicated patients with MDD and 16 healthy volunteers. Whereas IL-6 levels normalized again during the recovery night in depressed patients, they were still elevated in control subjects. Serum levels of IL-1RA were higher in depressed patients than in controls, but were not affected by TSD. During recovery sleep, IL-1RA levels increased as compared with the preceding TSD night only in controls. Responders (N=8) differed from nonresponders (N=7) to TSD with regard to IL-1RA, which increased significantly during TSD in responders only. Sleep deprivation therefore seems to significantly affect cytokine levels in both depressed patients and healthy subjects, but does so in different ways. Sleep disturbances in depressed patients could account for the increased levels of cytokines found in these patients in several previous studies. The interaction between antidepressant effects of TSD and alterations of cytokines warrants further investigation.

Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity

Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type 1 (HTLV-1). Indoleamine 2,3-dioxygenase (IDO), the l-tryptophan ( l-TRP)-degrading enzyme, plays a key role in the powerful immunomodulatory effects of several different types of immune cells. In this study, we investigated the IDO expression in ATLL cells and the effect of chemotherapy on IDO-initiating l-TRP catabolism in patients with ATLL. Serum l-kynurenine ( l-KYN) concentrations, l-KYN/ l-TRP ratio, and the level of IDO mRNA expression in ATLL cells were significantly increased in ATLL patients compared to those in healthy and HTLV-positive carrier subjects. On the other hand, l-TRP level was significantly decreased in ATLL patients compared to that in healthy subjects. In the immunohistochemical staining, IDO was strongly expressed in cytoplasm of ATLL cells. Interestingly, serum l-KYN as well as soluble IL-2 receptor concentrations was significantly reduced, and l-TRP concentrations were significantly increased after chemotherapy. These data provide evidence that IDO is highly expressed in ATLL cells, and that IDO-initiating l-TRP catabolism changes with chemotherapy.

Phenotyping Sarcoidosis from a Pulmonary Perspective

Sarcoidosis is known as a disease with high heterogeneity in clinical severity and inflammatory activity. On the basis of radiologic criteria, John Guyette Scadding developed a classification system, which is widely used, but is insufficient for clinical decision making. Therefore, biomarkers and genetic markers that predict outcome are urgently needed. To obtain a classification system based on clinical criteria to evaluate biomarker and genetic markers. We developed a protocol for classification of various disease courses (sarcoid clinical activity classification [SCAC]) based on clinical criteria with three categories: (1) whether the disease was acute or nonacute in onset, (2) whether treatment was required, and (3) whether there was need for long-term treatment. In total, we evaluated 225 patients with sarcoidosis, applying both classification protocols retrospectively. The described SCAC protocol based on clinical criteria was retrospectively able to stratify patients according to disease outcome. The classes of patients with chronic disease differed significantly regarding pulmonary function test parameters and bronchoalveolar lavage fluid cell composition. Most interestingly, concentrations of soluble IL-2 receptor and neopterin were particularly increased in patients with acute disease who required long-term treatment. A moderate but significant increase in soluble IL-2 receptor and neopterin was also observed in patients with nonacute disease who needed long-term treatment. In contrast to the clinical classification system, the system based on radiologic criteria separated the patients with the need for long-term therapy insufficiently, but identified patients with advanced fibrotic remodeling. The described SCAC protocol is practicable and gives additional information not yet acquired by radiologic typing and seems suitable for studies evaluating genetic influence and biomarkers.

Fish Oil Supplementation Modulates Immune Function in Healthy Infants

(n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 × 2 intervention in 64 healthy Danish infants, who received cow’s milk or infant formula alone or with fish oil (FO) (3.4 ± 1.1 mL/d) from 9 to 12 mo of age. Before and after the intervention, fatty acid composition of erythrocyte membranes, plasma IgE, C-reactive protein, and soluble IL-2 receptor concentrations were measured. TNF-α, INF-γ, and IL-10 concentrations in whole-blood cultures, stimulated for 22 h with LPS+phytohemaglutinin (PHA) or Lactobacillus paracasei, were also determined. IgA was measured in feces when infants were 10 mo of age. FO supplementation effectively raised erythrocyte (n-3) PUFA (P < 0.001), increased L. paracasei-induced INF-γ (P = 0.05) and tended to reduce LPS+PHA-induced IL-10 (P = 0.08). The FO intervention did not affect any of the other analyzed immune variables. The erythrocyte content of eicosapentanoic acid was negatively associated with LPS+PHA-induced IL-10 (r = −0.38, P = 0.02). Feeding milk rather than formula did not affect cytokine production, but plasma soluble IL-2 receptor concentration was greater in the formula group than in the cow’s milk group (P = 0.03). Since the capacity to produce INF-γ has been proposed as a maturation marker for the immune system in early life, this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation. The implications for later health need further investigation.

Modern management of children with haemophagocytic lymphohistiocytosis.

Modern management of children with haemophagocytic lymphohistiocytosis.

Preliminary evaluation of soluble IL-2 receptor and type III procollagen N-terminal aminopeptide in pleural fluid for differentiating tuberculous, carcinomatous and parapneumonic pleural effusions.

The aim of the study was to clarify the possibility of using pleural fluid levels of soluble IL-2 receptor (sIL-2R) and type III procollagen N-terminal aminopeptide (PIIIP) for differentiating tuberculous, carcinomatous and parapneumonic pleural effusions. Fifty patients with pleural effusions were investigated retrospectively. The pleural effusions were due to tuberculosis (n = 11), carcinoma (n = 22), pneumonia (n = 9) and heart failure (n = 8). The concentrations of sIL-2R and PIIIP were measured in pleural effusion using commercially available kits. Soluble IL-2 receptor concentrations were highest in the patients with tuberculosis (6,856 +/- 3,212 U/mL), followed by those with carcinoma (4,680 +/- 1,872 U/mL), pneumonia (2,227 +/- 525 U/mL) and heart failure (1,439 +/- 244 U/mL). Significant differences were found between tuberculosis and carcinoma (P = 0.023), carcinoma and pneumonia (P = 0.015), and pneumonia and heart failure (P = 0.002) groups. Type III procollagen N-terminal aminopeptide concentrations were higher in the patients with tuberculosis (262.5 +/- 157.9 U/mL) and pneumonia (257.0 +/- 96.7 U/mL) than in those with carcinoma (48.0 +/- 27.7 U/mL) and heart failure (10.9 +/- 5.6 U/mL). Significant differences were found between tuberculosis and carcinoma (P < 0.001) and pneumonia and carcinoma (P < 0.001). To differentiate effusions, the cutoff points of sIL-2R (2,980 U/mL) and PIIIP (110.0 U/mL) were obtained from the highest concentration in the pneumonia group and in the carcinoma group, respectively. Using these criteria, the sensitivities for differentiating tuberculous, carcinomatous, and parapneumonic effusions were 90.9, 86.4 and 88.9%, respectively, with 100, 95 and 100% specificity, respectively. The simultaneous determination of sIL-2R and PIIIP concentrations in pleural effusions may be clinically useful in differentiating tuberculous, carcinomatous, and parapneumonic effusions. Further assessments are required to determine the broad clinical application of this assay.

A prospective study of inflammation markers in patients at risk of indirect acute lung injury.

Systemic inflammation triggered by insults like sepsis and acute pancreatitis may play a role in development of indirect acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Because little is known about the course of systemic inflammation on the days preceding diagnosis of ARDS, we prospectively monitored immune inflammatory status in 52 patients at risk and we assessed the presence of ALI and ARDS on day 7 after admission to the intensive care unit. On admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor concentrations were significantly higher in patients with subsequent ALI (n = 18) than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6 levels of ALI patients remained high and those of non-ALI patients decreased. None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did non-ALI patients, whereas among 14 patients with massive transfusion, respective findings in ALI and non-ALI patients were comparable. Results give credence to the view that systemic inflammation plays a role in development of ALI triggered by pancreatitis, but not in that by massive transfusion. This finding, if confirmed in studies with sufficient statistical power, suggests that the patients with massive transfusion do not necessarily benefit from novel biotherapies aimed at altering the course of systemic inflammation.

Serum-soluble IL-2 receptor and IL-6 levels in patients with melanoma.

Elevated soluble IL-2 receptor (sIL-2R) and IL-6 serum concentrations have been reported as adverse prognostic factors in several types of cancer. In order to determine whether these factors are predictive of metastatic progression in melanoma, sIL-2R and IL-6 levels were measured in sera from 172 patients with melanoma and 60 in healthy controls. Mean sIL-2R values were significantly higher in the patients than in normal controls and the highest values were observed in those that developed metastasis during follow-up. However, no correlation was found with the stage of the disease. Serum IL-6 levels were found to be correlated with age and sex, but not correlated with sIL-2R levels. Statistical analysis was based on logistic and Cox regression models. The factors considered were age, sex, stage, disease-free interval and serum sIL-2R and IL-6 levels. The analysis showed that only the sIL-2R value is significantly linked to metastatic progression. This finding suggests that high serum levels of sIL-2R could be a predictive factor of metastatic progression in malignant melanoma.

244 GM-CSF induced activation of T-lymphocytes and macrophages

The effect of GM-CSF infused after 7 g/m 2 cyclophosphamide (CTX) and 800 mg/m 2 carboplatinum (CBDCA) was evaluated in 16 (LGNHL, MM, HD) patients. Serum concentrations of soluble CD8 (sCD8) and soluble IL-2 receptor (sIL-2R) as well as circulating levels of IL-2, IFN-γ, neopterin, IL-1α, ILl-β, TNF-α and IL-6 were determined on day 0 and days +4, +10 and +16 post-GM-CSF and intracellular IL-2, IFN-γ, IL-1α, IL1-β, TNF-α and IL-6 on days 0 and +16. sIL-2 R rose from day +4 to day + 16 and reached twice basal values at 10 and 16 days after both CTX (2266 ± 904, 2292 ± 873 vs 1189 ± 608) and CBDCA (2225 ± 965, 2313 ± 1055 vs 1151 ± 518). Neopterin also rose and was maximum on day +16 (1.7 post-CTX, 1.6 post-CBDCA vs basal). Serum IL-1α concentrations varied little after CTX, but increased two-fold over basal values after CBDCA (39.3 ± 34.6 vs 15.8 ± 40.5). Serum IL-1β increased 1.3 on the 16th post-GM-CSF day after CTX and 1.8 after CBDCA. Serum TNF-α rose to 1.8 basal values on day +10 and to 3.5 on day +16 following CBDCA, but not after CTX. Changes in the other serum and intracellular indices studied were negligible. These results suggest that GM-CSF activates T-Iymphocytes and macrophages, but that their activation partially depends on the therapy that precedes administration of the growth factor.

Increased IgE-levels in bullous pemphigoid correlate to soluble low affinity Fc-II-receptor for IgE and soluble IL-2-receptor

Background Increased serum-IgE levels in patients with bullous pemphigoid (BP) are one of the well known immunological deviations in this autoimmune dermatosis.Aim and methods Since the mechanism that leads to an increase of IgE in BP is still unclear, we investigated serum-IgE levels and IgE regulating cytokines (soluble low affinity Fc II receptor for IgE, IL-4, IFN-g and soluble IL-2 receptor) in sera and blister fluids of 15 BP patients before and during treatment with immunosuppressants using an ELISA-technique.Results All 15 patients examined proved to have high IgE levels in blister fluids (>100 KU/l) and 13 of the 15 patients had elevated serum-IgE levels. Soluble low affinity Fc II receptor for IgE (sCD23R) was also increased in sera (7.9 ± 2.4 pg/ml) and ten fold higher in blister fluids (76.7 ± 15.3 pg/ml). Investigation of cytokines interfering with IgE production showed significantly increased levels of the soluble IL-2 receptor in sera whereas the concentrations of IL-4 and IFN-g revealed no significant differences compared to controls. In blister fluids we detected all the cytokines investigated. During treatment with immunosuppressants the elevated concentrations of sCD23R and soluble IL-2 receptor were reduced to normal values.Conclusions The results show a direct correlation between IgE levels, sCD23R and soluble IL-2-receptor concentrations and suggest a connection between increased IgE levels and T-cell activation in BP.

Analysis of disease distribution, activity and complications in the patient with inflammatory bowel disease.

Management strategies in Crohn's disease and ulcerative colitis should be based on up-to-date information on disease distribution, extent, activity and complications. A system of structured analysis is suggested, with separate consideration of destructive ulceration, inflammatory activity and other factors. Direct investigation of gut immunity by using whole gut lavage fluid (WGLF) is a valuable new technique of clinical investigation in IBD and related disorders. Recent studies have shown that the concentrations of plasma-derived proteins in WGLF provide objective measures of disease activity; and that this activity is a separate phenomenon from destructive ulceration and fibrosis. Neutrophils in the lumen can be in- investigated by cytology, or by assay of neutrophil elastase in WGLF. Cytokines and other immuno-regulatory mediators can also be detected. These new techniques can provide a description of intestinal immunity and inflammation, based on a non-invasive test of 2-4 h duration. Work in progress shows that patients who respond clinically to elemental diet treatment have unusually high concentrations of soluble IL2 receptor in WGLF; cytokine profiles may facilitate the selection of patients suitable for other new treatment modalities.

Serum interleukin-1 alpha and soluble interleukin-2 receptor concentrations in cystic fibrosis.

Interleukin (IL)-1 and IL-2 may participate in the systemic inflammatory response and hypergammaglobulinaemia observed in patients with cystic fibrosis. Thirty seven patients with cystic fibrosis were compared with 25 normal controls. High IgG and IgM concentrations were associated with more severe pulmonary disease. IL-1 alpha and soluble IL-2 receptor concentrations were higher in the cystic fibrosis group than in the controls and also correlated with concentrations of IgG and IgM. These results suggest that these cytokines may contribute to enhanced immunoglobulin synthesis and silent inflammatory activity in clinically stable patients with cystic fibrosis.