Serum Soluble IL-2 Receptor Levels Research Articles

Clinical Application Value of High-Frequency Ultrasound Combined with Detection of Serum High Mobility Group Box 1, Soluble IL-2 Receptor, and Thyroglobulin Antibody in Diagnosing Thyroid Cancer.

Objective The aim of this study is to explore the clinical application value of high-frequency ultrasound combined with detection of serum high mobility group box (HMGB-1), soluble IL-2 receptor (SIL-2R), and thyroglobulin antibody (TgAb) in diagnosing thyroid cancer. Methods By means of retrospective study, 50 thyroid cancer patients treated in our hospital from January 2019 to January 2021 were selected as the thyroid cancer group, 50 patients with benign thyroid lesions were included in the benign lesion group, and 50 healthy individuals examined in our hospital in the same period were included in the control group. All study objects received high-frequency ultrasound examination, and at the same time, their serum HMGB-1, SIL-2R, and TgAb levels were measured. After that, the results of high-frequency ultrasound examination were analyzed, the diagnostic efficacy of different diagnosis methods was explored, and receiver operating characteristic (ROC) curves were plotted. Results According to the results of high-frequency ultrasound examination, there were significant differences in echogenicity surrounding and inside the lesion, calcification, blood flow distribution, and blood flow parameters between the thyroid cancer group and the benign lesion group (P < 0.001); the HMGB-1, SIL-2R, and TgAb levels were statistically different among the three groups (P < 0.001), and the level values of HMGB-1, SIL-2R, and TgAb of the thyroid cancer group were, respectively, (12.26 ± 1.32) ng/ml, (108.65 ± 9.75) pmol/L, and (690.65 ± 34.47) IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb were, respectively, 98.0%, 95.0%, 90.7%, and 99.0%, and AUC (95%CI) = 0.965 (0.931–0.999). Conclusion High-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb has a good value in diagnosing thyroid cancer, which should be promoted in practice.

Abatacept Use Is Associated with Steroid Dose Reduction and Improvement in Fatigue and CD4-Dysregulation in CVID Patients with Interstitial Lung Disease

Interstitial lung disease (ILD) represents a severe clinical manifestation of systemic immune dysregulation in patients with common variable immunodeficiency (CVID). Its treatment often requires systemic immunosuppression beyond corticosteroids. To assess the safety and efficacy of abatacept in patients with CVID and ILD. Ten patients with confirmed diagnosis ofCVIDand ILD were included in a single-center, prospective, open-label, nonrandomized trial. Abatacept was administered subcutaneously at a dose of 125 mg/wk for 12 months. Abatacept was a safe treatment for ILD in CVID except for 1 case of bronchopulmonary aspergillosis. One additional patient terminated the trial prematurely because of recurrent bronchitis. Five of 8 patients treated per protocol benefited from the treatment according to American ThoracicSociety/European Respiratory Society criteria. The primary end point of the study was met because single breath diffusing capacity of the lung for carbon monoxide was stable (62.5%) or improved (37.5%) in all patients treated per protocol. Although nodules (71%) and ground-glass opacities (57%) improved in most patients, other computed tomographypathologies were less responsive. Quality of life improved in 87.5% and fatigue in 57% of patients. Abatacept treatment was associated with significant improvement in CD4 T-cell dysregulation, signified by a decrease in serum soluble IL-2 receptor levels and of proliferating Ki67+ CD4 T cells, and a recovery of total lymphocytes, CD4+ T cells, and naive CD4 T cells. Abatacept may represent a treatment option for CVID-associated ILD. This pilot study demonstrated a good safety profile, steroid-sparing effect, positive immune modulation, and overall positive treatment response especially in quality of life. Larger controlled studies are needed to confirm these findings.

Are soluble IL-2 receptor and IL-12p40 levels useful markers for diagnosis of tuberculous pleurisy?

Background: The differential diagnostic utilities of the levels of soluble interleukin (IL)-12p40 and the IL-2 receptor in sera and pleural effusions were evaluated in patients with exudative pleural effusions. Methods: We enrolled a total of 120 patients with exudative pleural effusions. The clinical, radiological, and histopathological diagnoses were tuberculous pleurisy in 52, malignant pleurisy in 39, and parapneumonic effusions in 29 patients. Results: We measured serum IL-12p40 and adenosine deaminase (ADA) levels in patients with tuberculous pleurisy and in a control group treated for pleural effusion to determine if such levels were useful in the diagnosis of pleural effusion (p < 0.005). Definite microbiological or histopathological diagnoses of tuberculous pleurisy or pleural effusion were recorded, and we found that ADA and serum soluble IL-2 receptor levels aided in diagnosis (p < 0.001). The levels of ADA and soluble IL-2 in pleural effusions afforded sensitivities and specificities of 84.62% and 82.69% and of 70.59% and 80.88%, respectively. The soluble IL-2 receptor level afforded a sensitivity and specificity of 82.69% and 52.9%. IL-12p40 levels in pleural effusions and sera afforded sensitivities and specificities of 80.77% and 80.77% and of 60.29% and 39.71%, respectively. Conclusion: Soluble IL-2 receptor levels in patients with tuberculous pleurisy serve as markers of disease in non-endemic countries, similarly to ADA levels.

Prospective measurement of Epstein-Barr virus–DNA in plasma and peripheral blood mononuclear cells of extranodal NK/T-cell lymphoma, nasal type

AbstractEpstein-Barr virus (EBV)–DNA was prospectively analyzed in plasma and mononuclear cells (MNCs) from peripheral blood in patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type, to evaluate the clinical significance for diagnosis, monitoring the tumor burden, and prognostication. Thirty-three patients were enrolled, and 32 were evaluable. Pretreatment plasma and MNC EBV-DNA was detectable in 14 (range, 50-71 000 copies/mL) and 6 patients (range, 20-780 copies/μg DNA), respectively, and both were well correlated (r = 0.8741, P < .0001). Detectable plasma EBV-DNA was associated with higher clinical stage (P = .02), presence of B symptoms (P = .02), worse performance status (P = .02), and higher serum soluble IL-2 receptor level (P < .0001). Twenty-two patients attained complete response. Plasma EBV-DNA level was significantly higher in nonresponders than in responders (mean, 16 472 vs 2 645 copies/mL; P = .02). Multivariate analysis showed clinical stage (hazard ratio, 9.0; 95% confidence interval, 1.8%-45.0%) and pretreatment plasma EBV-DNA (hazard ratio, 10.6; 95% confidence interval, 1.3%-87.0%) were significant prognostic factors. Three-year overall survival of plasma EBV-DNA positive and negative patients was 42.9% and 94.4%, respectively (P = .0009). Plasma was a preferable sample for this purpose in NK/T-cell lymphoma, nasal type, and EBV-DNA level was a good indicator for response and overall survival.

Eotaxins and CCR3 Interaction Regulates the Th2 Environment of Cutaneous T-Cell Lymphoma

CC chemokine receptor 3 (CCR3), the sole receptor for eotaxins, is expressed on eosinophils and T helper type 2 (Th2) cells. In Hodgkin's disease, eotaxin-1 secreted by fibroblasts collects Th2 cells and eosinophils within the tissue. Similarly, many Th2 cells infiltrate the lesional skin of cutaneous T-cell lymphoma (CTCL). In this study, we investigated the role of eotaxins in the development of the Th2 environment of CTCL. We revealed that fibroblasts from lesional skin of CTCL expressed higher amounts of eotaxin-3 messenger RNA (mRNA) compared with those from normal skin. Lesional skin of CTCL at advanced stages contained significantly higher levels of eotaxin-3 and CCR3 mRNA, compared with early stages of CTCL. IL-4 mRNA was expressed in some cases at advanced stages. Immunohistochemistry revealed that keratinocytes, endothelial cells, and dermal fibroblasts in lesional skin of CTCL showed a stronger expression of eotaxin-3 than did normal skin. CCR3(+) lymphocytes and IL-4 expression were observed in some cases of advanced CTCL. Furthermore, both serum eotaxin-3 and eotaxin-1 levels of CTCL patients at advanced stages were significantly higher than those of healthy individuals. The concentrations of these chemokines correlated with serum soluble IL-2 receptor levels. These results suggest that interaction of eotaxins and CCR3 regulates the Th2-dominant tumor environment, which is closely related to the development of CTCL.

A multivariate analysis for the survival of nodal peripheral T-cell lymphoma (PTCL)

e19521 Background: Nodal peripheral T-cell lymphoma (PTCL) is uncommon lymphoma with various subtypes and poor prognosis. There is no definitive therapeutic improvement by conventional chemotherapy (CT) for decades. However, the superiority of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has remained inconclusive. The infrequency of PTCL is an obstacle to perform a large prospective study. We conducted a retrospective study of fifty six patients with three major nodal PTCL, histologically classified as PTCL-not specified (NOS, n=29), angioimmunoblastic T-cell lymphoma (AITL, n=19), and ALK-negative anaplastic large cell lymphoma (ALCL, n=8) who underwent ASCT (n=14) or not (n=42) after CT in Tokai University Hospital, Ebina General Hospital, and Hadano Red Cross Hospital, Kanagawa, Japan between 1997 and 2008. We determined whether international prognostic index (IPI), serum soluble IL-2 receptor level (sIL-2R) and ASCT were correlated with the survival. Methods: Retrospective, multicenter cohort study by time-dependent or non-time-dependent multivariate survival analysis with Cox proportional hazard regression. Results: Median age was 61 (18–81). The percentage of IPI more than 3 was 50. Median sIL-2R was 4120 ng/ml. (311–96,800). In non-time-dependent analysis, both ASCT and sIL-R were significant prognostic factors for overall survival (OS). Hazard ratio (HR) of ASCT, IPI, and sIL-2R were 0.24 (95%CI: 0.08–0.76, p=0.02), 0.77 (95%CI: 0.34–1.77, p=0.54), and 1.45 (95%CI: 1.129–1.857, p=0.035), respectively. But in time-dependent manner, the significant effect of ASCT was offset for OS. HR of ASCT was 0.82 (95%CI: 0.25–2.71, p=0.75). Only sIL-2R was still statistically significant, which HR was 1.31 (95%CI: 1.04–1.66, p=0.03). On the other hand, ASCT was only important effect on progression-free survival (PFS) by non-time-dependent analysis, which HR was 0.20 (95%CI: 0.07–0.55, p=0.02). After time-dependent analysis, no variates influenced PFS. Conclusions: The OS advantage of high-dose chemotherapy followed by ASCT is offset by time-dependent Cox proportional hazard analysis. The level of sIL-2R has impact on OS. Prospective multicenter randomized trial will be needed to show or not to show an advantage for ASCT. No significant financial relationships to disclose.

Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy.

Immunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoma. They received Cisplatin (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-alpha; Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n = 19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R) study, the percentage of cells expressing Tac (p55) receptor did not change either for healthy volunteers (n = 20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy, we observed a significant increase (P = 0.001) in patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.

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.

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.)

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.)

Immunomodulatory Effects of IL-12 in Relation to the Pineal Endocrine Function in Metastatic Cancer Patients

In addition to IL-2, IL-12 would constitute one of the most promising cytokines in the treatment of human neoplasms. IL-2 has been proven to induce in vitro and in vivo several evident changes in the secretion of cytokines and various other immunoinflammatory substances. In contrast, very litte data are available about the immune effects of IL-12 in humans. The present study was carried out to investigate the in vivo immunoinflammatory effects of IL-12 by analyzing the secretions of neopterin, soluble IL-2 receptor (SIL-2R), tumor necrosis factor α (TNF), IL-2 and IL-6 in relation to the neuroendocrine function of the pineal gland, which is one of the most important organs involved in neuroimmunomodulation. Pineal endocrine function was investigated by evaluating the whole daily urinary excretion of the main catabolite of its hormone melatonin, 6-sulfatoxymelatonin (6-MTS). The study was performed on metastatic renal cell cancer patients. Each course of IL-12 consisted of 1.25 µg/kg b.w. subcutaneously in the morning once a week for 3 consecutive weeks. The study evaluated 10 IL-12 courses. Mean serum levels of neopterin, SIL-2R and TNF significantly increased in response to IL-12, whereas no significant change occurred in IL-6 and IL-2 mean concentrations. Finally, 6-MTS urinary excretion was significantly reduced by IL-12 injection, particularly during the dark phase of the day. This preliminary study would suggest that IL-12 may induce important changes in the in vivo immunoinflammatory response. Moreover, IL-12 administration would suppress pineal endocrine activity, thus confirming its previously suggested involvement in the neuroimmunomodulatory processes. Because of the fundamental role of the pineal gland in neuroimmunomodulation, IL-12-induced immune variations could depend at least in part on its action at central neuroendocrine sites.

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.)

Circulating Soluble IL-2 Receptor Levels are Low in Patients with Hypothyroid Autoimmune Thyroiditis

In hypothyroid patients serum soluble IL-2 receptor levels showed scattered and conflicting results. In our report we studied circulating soluble interleukin 2 receptors in 22 patients with hypothyroid autoimmune thyroiditis before L-thyroxine treatment and when the patients became euthyroid. The mean of soluble Interleukin 2 receptor levels in the hypothyroid state was 48.6 pmol/l (95% confidence interval, 45.6-51.5) statistically lower than in the controls (95% confidence interval, 86.4 pmol/l, 83.3-89.4) (p < 0.0001). When the patients became euthyroid during L-thyroxine treatment, soluble Interleukin 2 receptor levels increased, showing mean values comparable to the controls. A positive high correlation (p < 0.001) was observed between soluble Interleukin 2 receptor levels and thyroxine free levels in the hypothyroid as well as in the euthyroid state and between soluble Interleukin 2 receptors and the mean weekly L-thyroxine dose. Our study confirmed that in the hypothyroid state, the behaviour of soluble Interleukin 2 receptors is anomalous as compared to other autoimmune diseases. In fact a strict relationship exists between the levels of thyroid hormones and soluble Interleukin 2 receptors but not between the latter and antithyroid antibodies. These results agree with those supporting a role for thyroid hormones in the regulation of the immune system. They also suggest that the measurement of soluble Interleukin 2 receptors could be used as a marker of the peripheral action of thyroid hormones.

Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies.

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.