Serum Soluble IL-2 Receptor Research Articles

Prognostic Value of Serum Soluble IL2 Receptor (sIL2R) Level in Patients with Diffuse Large B Cell Lymphoma (DLBCL), Treated with CHOP or R-CHOP Based Therapy.

Emergence of rituximab (R) has significantly changed the clinical outcome of patients with B-cell lymphoma, which necessitates investigators to reassess the roles of previously determined prognostic factors. We performed a retrospective study to clarify the prognostic significance of serum sIL2R levels among other factors in patients with DLBCL. Study group consisted of 208 consecutive untreated patients with DLBCL who had serum sIL2R levels examined prior to treatment, and were treated in our institution between January 1999 and December 2006. Patients were treated with CHOP based chemotherapy without (R-, n=112) or with (R+, n=96) rituximab. Median follow up duration of each group was 55 and 19 months, respectively. Age (18–92), performance status (PS, ≥2 or <2), B symptoms (present or absent), stage (1–4), number of extranodal involvement (≥2 or <2), bulky diseases (largest diameter of the disease ≥ 10cm, present or absent) serum LDH levels and sIL2R levels were available in all patients. Beta-2 microglobulin levels were available in 130 patients. Serum sIL2R levels ranged from 316 to 35100 U/mL (median 1080), while standard range in healthy individuals was <520 U/mL. Spearman correlation analyses revealed that Log sIL2R level (LsIL2R) was associated with age (p<0.001), PS (p<0.001), B symptoms (p<0.001), stage (p<0.001), number of extranodal involvement ≥2 (p<0.001), Log LDH level (LLDH) (p<0.001) and beta2 microlobulin (p<0.001). The impact of each factor on overall survival (OS) was analyzed by Cox proportional Hazard model. Univariate analyses revealed that age (Hazard ratio [HR]=1.034, p=0.010), stage (HR=1.357, p=0.021), B symptoms (HR=1.152, p<0.001), R− (HR=2.123, p=0.049), PS (HR=4.102, p<0.001), number of extranodal involvement ≥2 (HR=2.592, p<0.001), LsIL2R (HR=3.249, p<0.001), LLDH (HR=4.378, p<0.001) and beta2 microglobulin (HR=1.283, p<0.001) were associated with shorter OS. When analyses was performed separately in R− and R+ groups, HR of LsIL2R was 3.59 (p<0.001) and 2.92 (p=0.071), respectively. Multivariate analysis in the entire group revealed that age (HR=1.030, p=0.041), PS (HR=2.089, p=0.038), B symptoms (HR=2.307, p=0.022), R− (HR=2.721, p=0.038), and LsIL2R (HR=2.140, p=0.018) were independently associated with shorter OS. When multivariate analysis was performed in R− group alone, age (HR=1.035, p=0.035), B symptoms (HR=3.565, p=0.001), and LsIL2R (HR=2.704, p=0.004) independently correlated with shorter OS. In the group of R+, only PS was left as an independent prognostic factor (HR=5.304, p<0.001). When LsIL2R was put back into the multivariate model of R+ group, HR of PS and LsIL2R became 4.308 (p=0.035) and 2.383 (p=0.165), respectively. In conclusion, serum sIL2R levels are frequently elevated in untreated patients with DLBCL and the higher level is significantly associated with shorter OS, independent of other known prognostic factors. When analysis was limited to R+ group, known prognostic factors such as age were not deemed independently associated with OS possibly due to short follow up duration and excellent prognosis in this population (estimated 3-year OS rate of 88%); thus longer follow up of this large cohort is necessary. Updated analyses for OS and various different analyses, such as analyses for correlation with complete response or time to treatment failure will be presented to further clarify the value of sIL2R levels.

Urinary pseudouridine in patients with lymphoma: Comparison with other clinical parameters

Background Some patients with malignant lymphoma do not manifest superficial lymphadenopathy. In such cases, clinical parameters that indicate the number of tumor cells are important for the assessment of tumor growth and choice of proper treatment. We evaluated urinary pseudouridine (U-PU) as an indicator of the growth of malignant lymphoma by comparing its levels with serum concentrations of other clinical parameters in patients with various lymphomas at various stages. Methods Urine was obtained from 67 patients with lymphoma. U-PU was assayed by recombinant Fab-based inhibition ELISA. Serum soluble IL2 receptor (sIL2R), serum deoxythymidine kinase (dTK), serum beta-2 microglobulin (β2MG) and serum lactate dehydrogenase (LDH) were also assayed. Results U-PU concentrations showed good correlations with serum concentrations of β2MG, LDH, sIL2R and dTK. The level of U-PU was higher in stage IV than in stages I ( P = 0.023), II ( P = 0.006) and III ( P = 0.036). Conclusion U-PU concentration correlates with the clinical stage of lymphoma and is a useful tool to assess the growth of lymphoma.

高熱, リンパ節腫脹を繰り返したのち発症したHIV-1陽性HHV-8関連Castleman病の1例

A 48-year-old man infected with an HIV-1 experienced intermittent bouts of fever, lymphadenopathy, elevated CRP level, and thrombocytopenia, each lasting about 2 weeks, and recurring at 2-3 month intervals. His CD4 count was about 500/microL, and he had never received antiretroviral therapy (ART). In March 2005, he experienced the same symptoms, accompanied by liver damage, splenomegaly, pleural fluid, and a high serum soluble IL-2 receptor level. Examination of a cervical lymph node specimen resulted in a diagnosis of Castleman disease, plasma cell type. Immunohistochemical studies confirmed the presence of HHV-8 and Ebstein-Barr virus (EBV). Since the plasma HHV-8 DNA and serum IL-6 were elevated during the flare-up, were negative between episodes, he was treated with ART to control the Castleman disease. He remained asymptomatic for 3 months, but, similar symptoms recurred with a high level of HHV-8 DNA in his PBMCs. Oral valganciclovir was them started at 1,800 mg twice daily, and his symptoms immediately improved. The HHV-8 DNA level in the PBMCs decreased markedly over the course of 4 weeks, and valganciclovir was discontinued. One week later, he experienced another flare-up, and was successfully treated with 10 days of valganciclovir 1,800 mg, followed by maintenance with valganciclovir 900 mg. ART was discontinued, because the valganciclovir plus ART caused severe fatigue. No subsequent flare-ups have been observed, and, no HHV-8 DNA has been detected in his PBMCs. Castleman disease is an unusual complication in patients with HIV-1 and HHV-8 infection, but it should be included in the differential diagnosis of patients who exhibit a relapsing systemic inflammatory syndrome and lymphoadenopathy. Further study is needed to determine the appropriate usage and timing of the anti-HHV-8 and HIV-1 medication.

Sarcoidosis Associated with Renal Masses on Computed Tomography

A 50-year-old woman was admitted to our hospital after computed tomography (CT) revealed renal masses and mediastinal lymphadenopathy. Uveitis had previously been diagnosed by a local ophthalmologist. Elevated levels of serum soluble IL2 receptor were observed. However, renal function was not compromised. Abdominal CT showed multiple low attenuation tumor-like nodules in both kidneys. As lymphoma was considered likely, CT-guided renal biopsy was performed; however, histological examination of the excised specimens revealed noncaseating granulomas. Analysis of bronchoalveolar lavage fluid demonstrated a sarcoidosis pattern. The final diagnosis was sarcoidosis with renal involvement.

The effects of celecoxib augmentation on cytokine levels in schizophrenia

Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.

Effect of neuroleptic administration on serum levels of soluble IL-2 receptor-alpha and IL-1 receptor antagonist in schizophrenic patients

Activation of the inflammatory response system has been reported in schizophrenia. Levels of serum IL-1 receptor antagonist (IL-1ra) and soluble IL-2 receptor (sIL-2Rα) were studied in 32 schizophrenic and 22 age- and sex-matched healthy subjects before and after an 8-week treatment protocol. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). At weeks 0 and 8, sIL-2Rα levels were significantly higher than in the schizophrenic patients, as well as in a neuroleptic-naïve subgroup, than in controls. Patients' sIL-2Rα levels did not vary significantly between weeks 0 and 8. IL-1ra levels in controls did not differ significantly from those in patients at week 0 but were significantly lower at week 8. The patients' serum IL-1ra levels varied significantly between weeks 0 and 8. IL-1ra levels were significantly higher in the subgroup of neuroleptic-naïve patients at week 0 than in controls. Levels of sIL-2Rα at week 0 were positively correlated with PANSS positive and negative symptom scores at week 8, and levels at week 8 were positively correlated with PANSS total, positive symptom, and negative symptom scores at week 8. IL-1ra levels at week 0 were positively correlated with PANSS scores at week 8. There were positive correlations between both delta (baseline values minus endline values) IL-1ra and delta sIL-2Rα levels and delta PANSS negative symptoms. The results provide evidence for immune activation in some schizophrenic patients and suggest that medication differentially affects the production of sIL-2Rα and IL-1ra.

Serum Interleukin-12 Levels in Patients with Gastric Cancer

To evaluate the immunological status of patients with gastric cancer before surgery, we investigated the relationship between serum interleukin-12 (IL-12) levels and clinicopathological factors. We measured serum IL-12 levels in 127 patients with gastric cancer and 35 healthy controls, by a sandwich enzyme-linked immunosorbent assay using the Human IL-12 +p40 Immunoassay kit. The serum IL-12 levels in the patients with gastric cancer were significantly higher than those of the healthy controls (P < 0.05). There were no significant differences in disease stage or gross appearance among the cancer groups, but the serum IL-12 levels in patients with T4 disease were significantly lower than those in patients with T1, T2, or T3 (P < 0.01). There were no significant differences in serum IL-12 levels between patients with and those without lymph node, liver, or peritoneal metastasis. The serum IL-12 levels in patients with distant metastasis were significantly lower than those in patients without distant metastasis (P < 0.02). There were no significant differences in the serum IL-12 levels according to classification by histopathological findings. Analysis with the linear correlation coefficient showed no significant correlation between serum IL-12 and serum carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, CA 72-4, alpha-fetoprotein, or immunosuppressive acidic protein. However, there was a significant relationship between serum IL-12 levels and soluble IL-2 receptor levels (r = 0.53, P < 0.01). Serum IL-12 levels in patients with far-advanced gastric cancer were significantly lower than those in patients with less-advanced gastric cancer. This is because macrophages in patients with far-advanced cancer would be hectic and unable to produce sufficient IL-12.

High Incidence of Asian Variant Intravascular Large B-Cell Lymphoma (IVL) among IVL in Japan: Clinicopathologic Study of 95 Patients.

IVL is a rare form of aggressive B-cell lymphoma characterized by multifocal and predominant growth within vessels. Although its neurologic and dermatologic manifestations at diagnosis have been well documented, clinical courses of IVL are protean by patients. Systematic strategies for diagnosis and treatment of IVL are still to be established. To address these issues, we retrospectively analyzed a series of patients with IVL. This study was conducted by a refractory lymphoma study group, supported by the Ministry of Labor, Health and Welfare of Japan, and approved by the institutional review board of each participating institution. Both histopathological findings of IVL and positive reactions for at least one B-cell antigens (CD20, CD19 or CD79a) were required for inclusion. There were 95 patients (49 males and 46 females), with a median age of 67 years old (range 41–85). Most patients of IVL were associated with poor prognostic factors; i.e., 95% had more than 1 site of extranodal involvement, 91% had stage III/IV disease, 82% showed performance status greater than 1, and 94% had serum lactate dehydrogenase higher than normal level. Eighty-five percent was classified to the high-risk group of the International Prognostic Index (IPI). Therefore, IPI is not useful for the prognostification of IVL. Thirty-five patients (37%) were positive for CD5. Hemophagocytosis in the bone marrow, a key pathologic criterion for Asian variant of IVL (AIVL; Murase et al: Brit J Haematol 2000), was noted in 53 of 79 patients (67%) with available information. All these 53 patients met the clinical and laboratory criteria for AIVL, including anemia, thrombocytopenia, hepatosplenomegaly, and absence of tumor formation. In contrast, no hemophagocytosis was observed in 13 patients who did not meet the criteria. Patients with IVL were further characterized by the presence of B symptoms (76%), neurologic abnormality (27%), skin lesion (13%), and leukocytopenia (<4x109/L; 27%). Bone marrow involvement was identified in 76% of the patients. Leukemic lymphoma cells were noted in 28% of the patients. Since 16 patients were diagnosed at autopsy, and 4 died shortly after the diagnosis or failed to follow, 75 were enrolled for analyses of prognostic factors. Univariate analyses for overall survival showed no use of anthracycline containing regimen (p=0.001), older age (p=0.005), lower platelet count (<100x109/L; p=0.006), and higher serum soluble IL-2 receptor (5x103U/mL or more; p=0.017) as unfavorable prognostic factors. Multivariate analysis using Cox regression model revealed that all these three factors were independent and significant prognostic factors (no anthracycline regimen: p=0.002, Hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.53–6.90; age by 10 years: p=0.014, HR 1.36, 95%CI 1.07–1.66; and platelet <100x109/L: p=0.037, HR 2.12, 95%CI 1.05–4.31). These findings suggest patients with IVL should be treated chemotherapy containing anthracyclines.

Soluble interleukin 2 receptor (sIL‐2R) levels in renal transplant recipients

Allograft rejection is associated with T cell activation. T cell activation leads to secretion of soluble IL-2 receptor and elevated serum soluble IL-2 receptor (sIL-2R) levels. However, the clinical implication of individual elevated sIL-2 receptor levels is unclear. We followed levels of sIL-2R pre- and post-transplantation to determine if sIL-2R levels predict rejection episodes or degree of graft function. Serum samples of 12 patients who underwent living or cadaveric renal transplant were followed weekly with serial sIL-2R levels. These levels were followed until the serum creatinine reached a baseline. Of the 12 patients, three patients developed delayed graft function. The remaining nine patients were followed for a period of 3 months. Sera of these nine patients in the initial 3 months post-transplant were monitored for sIL-2R levels. For comparison, sIL-2R levels were also measured in 150 healthy volunteers and five dialysis patients. Recipients undergoing severe rejection episodes had higher overall serum levels of sIL-2R (1515 +/- 496 U/mL) as compared with recipients who had stable renal transplants and no episodes of rejection (698 +/- 333 U/mL) (P = 0.034). Comparison of sIL-2R ratios (post-transplant sIL-2R level/pre-transplant sIL-2R level) revealed that ratios of 0.6 or higher were more frequently seen in patients who subsequently underwent severe rejection episodes. Dialysis patients were found to have higher sIL-2R levels (2605 +/- 1312 U/mL) compared with renal transplant patients (1047 +/- 192 U/mL) (P < 0.001) and healthy volunteers (349 +/- 185 U/mL) (P < 0.001). Our results suggest that individual levels of sIL-2R are not predictive of rejection in the early post-transplant period, but s-IL2R ratios greater than 0.6 may be predictive of severe rejection episodes.

Relationship between coagulation cascade, cytokine, adhesion molecule and aortic aneurysm.

Patients with aortic aneurysm (AA) were in the chronic inflammatory condition and are often combined with disseminated intervascular coagulation. Recent studies demonstrated that atherosclerosis was inflammatory disease. AA and severe atherosclerosis with ulcer formation contain macrophages and T lymphocytes and accelerate the production of interleukin (IL)-2, which activates lymphocytes and lead to further adhesion of leukocytes. This study was designed to clarify the coagulation condition, cytokine, adhesion molecule, and collagen turnover in patients with AA and finally their relationship with the aneurysmal size. Thrombin-antithrombin III complex (TAT), plasma D-dimer, serum type III procollagen peptide (PIIIP), serum soluble IL-2 receptor (sIL-2R), Free tissue factor pathway inhibitor (TFPI), and soluble intercellular adhesion molecule (ICAM-1) were measured preoperatively around the same period when computed tomography (CT) was taken in 17 patients with AA (mean age: 72.2 years). Age-matched (mean age:70 years) volunteers were served as control. Maximum aneurysmal size was measured by CT and aneurysmal volume was also calculated from CT. AA patients showed significantly higher level in preoperative TAT and D-dimer compared to control (TAT: control 2.5+/-1.2 ng/ml, pre 7.2+/-4.5,ng/ml; P=0.0001; D-dimer: control 107+/-46 U/ml, pre 420+/-256 U/ml; P=0.0001). Cytokine also showed higher level preoperatively (sIL-2R: control 398+/-132 U/ml, pre 735+/-260 U/ml; P=0.0001). TFPI showed higher value preoperatively (control 22.9+/-4.9 ng/ml, pre 30.4+/-6.9 ng/ml; P=0.003). PIIIP (collagen turnover) showed no difference between the groups (P=0.0057) and neither did ICAM-1(P=0.0087). TAT (r=0.799, P=0.0001), D-dimer (r=0.56, P=0.0193), sIL-2R (r=0.709, P=0.0021), PIIIP (r=0.561, P=0.00239), and sICAM-1 (r=0.505, P=0.046) level showed positive correlation with aortic aneurysmal size and also TAT D-dimer, and sIL-2R levels were positively correlated with aneurysmal volume (r=0.714 P=0.0013, r=0.556 P=0.00204, r=0.693 P=0.0029, respectively). AA patients were in the hypercoagulation and inflammatory condition. Aneurysmal size was well correlated with TAT, D-dimer, sIL-2R, PIIIP, and sICAM-1, suggesting that these markers could be good diagnostic and monitoring tool for the disease progression.

Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris

Background: Both atopic dermatitis (AD) and psoriasis vulgaris (PsV) are characterized as chronic and relapsing inflammatory skin diseases associated with various immunologic abnormalities. Cutaneous T cell-attracting chemokine (CTACK; CCL27) is a member of the CC chemokine family and a functional ligand for CC chemokine receptor 10. It is selectively expressed in skin and attracts CC chemokine receptor 10-expressing skin-homing memory T cells. The epidermal keratinocyte is a main source of CTACK, suggesting the involvement of various inflammatory skin diseases. Objective: The purpose of this investigation was to clarify whether CTACK produced by keratinocytes is detected in the sera of patients with AD and PsV and to examine the correlation between the serum CTACK levels and disease activity of patients with AD and PsV. Methods: We measured the serum CTACK levels in 50 patients with AD, 30 patients with PsV, and 22 healthy control subjects. We also divided 50 patients with AD into 3 groups (ie, those with mild, moderate, and severe disease) and compared them among 3 categories. Moreover, we compared the serum CTACK levels of patients with AD and PsV with clinical or laboratory data. Immunohistochemical staining of CTACK and IFN-induced protein of 10 kd (IP-10; CXCL10) was performed on the lesional skin of patients with AD and PsV. Results: The serum CTACK levels in patients with AD and PsV were significantly higher than those in healthy control subjects. The serum CTACK levels in patients with AD significantly correlated with scoring atopic dermatitis (SCORAD) scores, serum soluble IL-2 receptor levels, serum soluble E-selectin levels, serum thymus and activation-regulated chemokine levels, and serum macrophage-derived chemokine levels. Serum CTACK levels in patients with PsV significantly correlated with the serum IP-10 levels but not with the Psoriasis Area and Severity Index score. Immunohistochemical staining showed CTACK was strongly expressed in lesional ke-ratinocytes of patients with AD and PsV, whereas IP-10 was strongly expressed in lesional keratinocytes of patients with PsV and focally in those with AD. Conclusion: These results suggest that CTACK might be one of the important chemokines for the pathogenesis of AD and PsV. (J Allergy Clin Immunol 2003;111:592-7.)

High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder

Background Previously, we found an increased prevalence of thyroid autoantibodies in patients with bipolar disorder. In the present study, we investigated other signs of immune activation in bipolar patients, in particular an activation of the T cell system. Methods Fluorescence activated cell scanning (FACS) analysis was performed on lymphocytes of 64 outpatients with DSM-IV bipolar disorder using the T cell marker CD3 in combination with the activation markers MHC-class II, CD25, CD69 or CD71. In 34 patients, these assays were repeated after an interval of 2 years. In addition, T cell activation was determined by measuring serum soluble IL-2 receptor (sIL-2R) in 172 bipolar outpatients. Outcomes were compared with a healthy control group. Results Significantly higher numbers of circulating activated T cells and raised sIL-2R levels were found in euthymic, manic, and depressed bipolar patients when compared with healthy controls. In general, these abnormalities were stable over time. Manic patients showed significantly higher levels of sIL-2R in comparison with depressed patients. Conclusions The T cell system was found to be activated in both symptomatic and euthymic patients with bipolar disorder. The pathophysiological significance of these findings remains to be explored.

Serum cytokine levels in atopic dermatitis.

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.

EBV Associated Hemophagocytic Syndrome Accompanied by Central Pontine Myelinolysis

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patient's central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methyl-predonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.

Serum and ascites fluid cytokine levels in patients with chronic heart failure

Objective — Cytokines that are capable of modulating cardiovascular function were reported to be elevated in patients with advanced heart failure.We evaluated the diagnostic importance of cytokines both in the serum and ascites.Material and methods — We determined serum and ascites fluid TNF-α, IL-1β, IL-6, IL-8, and soluble IL-2 receptor levels in 14 patients with congestive heart failure (group 1) and in 15 patients with chronic liver disease (group 2).Results — Ascites fluid IL-8 and soluble IL-2 receptor levels were found to be significantly elevated in group 1 when compared with group 2 (p = 0.014 and p = 0.005). There were no statistical differences in serum TNF-α, IL-1β, IL-6, IL-8, and soluble IL-2 receptor levels and ascites fluid TNF-α, IL-1β, and IL-6 levels.Ascites fluid/serum IL-1b and IL-8 ratio was lower in group 1 when compared with group 2 (p = 0.001 and p = 0.005). Ascites fluid/serum IL-2 and IL-6 ratio was higher in group 1 when compared with group 2 (p = 0.035 and p = 0.025).Conclusion — Cytokine levels in ascites fluid, but not in serum, are important in congestive heart failure. Ascites fluid/serum cytokine level ratios were detected to be more conclusive and valid in the diagnosis work-up of ascites aetiology.

The predictive value of serum interleukins in recurrent respiratory papillomatosis: a preliminary study.

IL-2 is the primary interleukin responsible for activation of the cell-mediated (Th1) arm of the immune response. Our objective was to determine whether a correlation existed between circulating levels of interleukin-2 as well as its soluble receptor (sIL-2R) and the clinical course of recurrent respiratory papillomatosis. Fifteen children with a histological diagnosis of RRP were recruited. Age at the time of study, time since first diagnosis, and number of surgical interventions were recorded. The number of surgically treated recurrences per year was then calculated. We obtained serum samples from each of these 15 children and from 10 normal control subjects. We then performed in vitro determination of serum IL-2 and soluble IL-2 receptor levels using enzyme-linked immunosorbent assay (ELISA) techniques. IL-2 was significantly lower (136.6 vs. 199.9 pg/mL, P =.035) in papilloma patients than in control subjects. IL-2R was also lower in papilloma patients (531.7 vs. 785.8 U/mL, P =.025). There was no statistical age difference between the papilloma and control groups. Among patients with papillomatosis, IL-2 and sIL-2R levels were significantly higher in those with aggressive disease (>4 surgically treated recurrences per year) versus non-aggressive disease (179.2 vs. 99.2 pg/mL, P =.024; and 697 vs. 387 U/mL, P =.022). Age was also significantly lower in the aggressive papilloma group (P =.002). Levels of interleukin-2 and IL-2 receptor were significantly lower in patients with recurrent respiratory papillomatosis compared with normal children. These data support the presence of an aberrant cell-mediated immune response in children with recurrent respiratory papillomatosis.

Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of TH2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4–positive (CCR4+) or CCR8+ cells. Objective: The purpose of this study was to investigate the participation of TARC in AD. Methods: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. Results: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in ke-ratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. Conclusion: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD. (J Allergy Clin Immunol 2001;107:535-41.)

IL-18 might reflect disease activity in mild and moderate asthma exacerbation

Background: IL-18, identified as an IFN-γ–inducing factor, is a proinflammatory cytokine that plays an important role in TH1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines. Objective: The aim was to evaluate the contribution of IL-18 to asthma exacerbation. Methods: Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-γ levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy. Results: Significantly higher serum IL-18 levels were found in patients with acute asthma (215 ± 33 pg/mL, mean ± SE; P = .02) and pulmonary sarcoidosis (239 ± 27 pg/mL, P = .008) than in control subjects (127 ± 11 pg/mL), but the plasma IFN-γ level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-γ levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy. Conclusion: It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation. (J Allergy Clin Immunol 2001;107:331-6.)

Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-γ in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation

Background: Acute graft-versus-host disease still represents the major factor that limits successful allogeneic bone marrow transplantation. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease. Objective: This study was performed to investigate whether the serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-γ were associated with the manifestation of acute graft-versus-host disease. Methods: Serum cytokine levels were measured by sandwich ELISA in 18 patients who underwent allogeneic bone marrow transplantation. Results: Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-γ were increased in patients in whom acute graft-versus-host disease developed. However, only serum soluble IL-2 receptor levels were significantly related to disease severity. Serum levels of IL-12 and IL-18, both of which are mainly produced by activated macrophages, were increased in different phases of acute graft-versus-host disease, especially grade I. Serum levels of soluble IL-2 receptor and IFN-γ were significantly elevated in patients with fever. Conclusion: Serum levels of soluble IL-2 receptor were more closely related to the severity of acute graft-versus-host disease than those of IL-12, IL-18, and IFN-γ. (J Allergy Clin Immunol 2000;106:S45-50.)

Increased frequency of interferon-gamma-producing peripheral blood CD4+ T cells in chronic hepatitis C virus infection.

To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-gamma and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-gamma and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. The frequency of IFN-gamma producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p<0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-gamma-producing cells. In HCV infected subjects, both serum sIL-2R and IFN-gamma are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection.