Increased Level of Soluble Interleukin-2 Receptor in Advanced Solid Tumors: A Preliminary Study

1988 ◽  
Vol 74 (6) ◽  
pp. 633-637 ◽  
Author(s):  
Franco Rovelli ◽  
Paolo Lissoni ◽  
Sergio Crispino ◽  
Sandro Barni ◽  
Gabriele Fumagalli ◽  
...  

Both activated normal and transformed lymphocytes produce not only cell-associated but also cell-free IL-2R. Evidence of high serum concentrations of IL-2R appears to serve as a tumor marker in patients with lymphomas On the contrary, the role of soluble IL-2R in solid neoplasms has still to be defined. This investigation was carried out to analyze soluble IL-2R production in human solid tumors. The study included 35 patients with solid tumors (12 without and 23 with metastases), 58 healthy subjects and 6 lymphoma patients. Among cancer patients, lung and breast carcinoma were the two most frequent neoplasms. In each subject or patient, serum levels of IL-2R were measured by using an enzyme immunoassay. Moreover, in 14/23 patients with metastatic solid tumors, lymphocyte subpopulations were also evaluated. Serum levels of IL-2R were significantly higher in the cancer patients than in the normal subjects. The patients with metastatic solid tumors showed significantly higher mean levels than those without metastases, and similar to those observed in the lymphoma patients. Finally, there was no correlation between serum levels of IL-2R and the T4/T8 ratio, which was reduced in 5/14 cancer patients. Further studies will be needed to establish if elevated concentrations of IL-2R in the serum can contribute to the immunoincompetence of patients with disseminated solid neoplasms.

1989 ◽  
Vol 4 (4) ◽  
pp. 203-206 ◽  
Author(s):  
P. Lissoni ◽  
S. Viviani ◽  
A. Santoro ◽  
S. Barni ◽  
G. Tancini

In order to investigate the production of interleukin-2 (IL-2) in human neoplasms, we determined IL-2 and soluble IL-2 receptors (sIL-2R) in serum from 18 patients with lymphoma and 28 patients with solid tumors, with (15 cases) or without (13 cases) metastases. As controls, 58 healthy subjects were evaluated. Low levels of IL-2 were not observed in patients with lymphoma or limited solid tumor but abnormally low concentrations of IL-2 were seen in 4/15 metastatic solid tumors, associated with abnormally high values of sIL-2R. This preliminary study confirms in vivo the reduced IL-2 production in metastatic solid neoplasms, previously documented in vitro


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 424-429 ◽  
Author(s):  
DP Barton ◽  
DK Blanchard ◽  
B Michelini-Norris ◽  
SV Nicosia ◽  
D Cavanagh ◽  
...  

Abstract This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.


1996 ◽  
Vol 24 (3) ◽  
pp. 239-245 ◽  
Author(s):  
H Simsek ◽  
A Kadayifci

T lymphocytes produce interleukin 2 (IL-2) associated with the expression of a soluble receptor for IL-2 (sIL-2R) on the surface of the cells, and these cytokines may contribute to hepatic injury in chronic active hepatitis C (CAH-C). Serum IL-2 and sIL-2R levels were analysed by enzyme linked immunosorbent assay in 22 patients (eight female, 14 male, mean age 42.6 years) with CAH-C. Eight patients had been given interferon α-2a (IFN α-2a), 3 million international units, three times weekly, for a mean of 12 weeks while the others were not on treatment. Serum IL-2 levels were 60.8 ± 9.5 pg/ml, 66.6 ± 5.7 pg/ml and 59.1 ± 4.0 pg/ml in the treated patients, untreated patients and controls, respectively. Serum sIL-2R levels were 1631 ± 194 pg/ml, 4016 ± 1076 pg/ml and 1169 ± 115 pg/ml in treated patients, untreated patients and controls, respectively. There were no significant differences in serum IL-2 levels between the groups ( P > 0.05) while a significant difference was found in serum sIL-2R levels between untreated patients and controls (P = 0.0032). Serum sIL-2R levels were lower in patients treated with IFN α-2a than in untreated patients but this difference was not statistically significant. This preliminary study indicates that there are no significant changes in serum IL-2 levels in CAH-C patients, but that sIL-2R concentrations are raised in untreated patients though not in treated patients. High serum sIL-2R concentrations may have a role in the pathogenesis of CAH-C.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 424-429 ◽  
Author(s):  
DP Barton ◽  
DK Blanchard ◽  
B Michelini-Norris ◽  
SV Nicosia ◽  
D Cavanagh ◽  
...  

This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.


1992 ◽  
Vol 6 (4-5) ◽  
pp. 385-388 ◽  
Author(s):  
Giovanni Pizzolo ◽  
Friederike Dallenbach ◽  
Fabrizio Vinante ◽  
Lorella Morosato ◽  
Donata De Sabata ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1093.1-1093
Author(s):  
G. Pellegrino ◽  
K. Stefanantoni ◽  
F. Facioni ◽  
C. Angelelli ◽  
A. Gigante ◽  
...  

Background:Electrocardiographic (ECG) abnormalities are described in 25-75% Systemic Sclerosis (SSc) cases and they are associated with other systemic manifestations as well as with a worse prognosis. There is an increasing need for clinical and laboratory biomarkers to ameliorate the diagnostic and therapeutic approaches to patients with ECG abnormalities, due to their actual low sensitivity and specificity. Adipokines are circulating proteins that appear dysregulated in SSc and leptin in particular is synthesized in response to inflammatory conditions and seems to play a proinflammatory and pro-fibrotic action in SSc. Interesting, many studies in the last years have underlined its role in the cardiac remodeling mechanisms and in the development of cardiac fibrosis in other chronic diseases.Objectives:Aim of our study is to evaluate the role of leptin in the development of cardiac rhythm disorders (CRD) during SSc. Furthermore, by the analysis of the clinical and demographical parameters of our SSc patients, we tried to define other possible features associated with increased serum leptin concentration.Methods:We included eighty-five SSc patients, fulfilling the 2013 ACR/EULAR classification criteria, attending the Regional Rare Disease Center of Policlinico Umberto I of Rome. Fifty presented significant CRD at non-invasive diagnostic techniques (12 Lead ECG, 24-hour Holter ECG). Demographic, clinical, conventional cardiovascular risk factors were examined; instrumental and laboratory assessments were obtained, together with ECG recordings. Thirty-five SSc patients without pathologic finding at ECG traces, matched for demographic and clinical features, were recruited as the control group. In all cases, after obtaining written informed consent, blood samples were taken to measure serum levels of leptin using an ELISA assay (Life Technologies-Italia).Results:The fifty SSc patients with CRD (mean age 51±15 years; F:M 41:9) had pulmonary fibrosis (PF) in 32 cases (64%) and a BMI >25Kg/m2in 22 (44%) while in the control group of thirty-five SSc patients (mean age 49±16 years; F:M 33:2) PF was found in 15 (43%) and a BMI >25Kg/m2in 9 (35%); We detected significantly higher median values of serum leptin in SSc patients with CRD compared to the control group (12027 pg/ml IQR 12314 versus 6392 pg/ml IQR 7103;p 0,0009). Additionally, SSc patients with a BMI> 25 kg/m2(31 cases) as well as those with PF (47 cases) showed a significantly higher median serum leptin levels compared to those with BMI <25 kg/m2(13161 pg/ml IQR 13610 versus 8187 pg/ml IQR 8255;p 0,0008) and those without PF (11740 pg/ml IQR 11940 versus 7616 pg/ml IQR 7855;p 0,0079).Conclusion:To our knowledge this is the first report on high serum levels of leptin in SSc patients with CRD that also confirms its increase in those cases with a BMI >25 kg/m2and with PF, according to scientific literature data. The role of leptin in the pathogenesis of SSc remains unclear although it is already known its involvement in the development of cardiac fibrosis during other chronic diseases. On the basis of these results we speculate on leptin involvement in the pathogenesis of CRD during SSc, although further studies are needed with larger cohort of patients.References:[1]Vacca A et al. Rheumatology, 2014[2]Tyndall AJ et al. Ann Rheum Dis, 2010[3]Muresan L et al. Iran J Pub Health, 2017[4]Sanna T et al. Indian Pacing Electrophysiol J, 2009[5]Riccieri V et al. Clin Exp Rheumatol, 2011[6]Żółkiewicz J et al. Arch Dermatol Res, 2019[7]Huby AC et al. Circulation, 2015[8]Shulze PC et al. Clin Chim Acta, 2005[9]Van de Hoogen F et al. Arthritis Rheum, 2013[10]Gui X et al. Biochem Biophys Res Commun, 2018Disclosure of Interests:Greta Pellegrino: None declared, Katia Stefanantoni Consultant of: ItalfarmacoBoehringer Ingelheim, Fausta Facioni: None declared, Carlotta Angelelli: None declared, Antonietta Gigante: None declared, Roberto Badagliacca: None declared, Carmine Dario Vizza: None declared, Sergio Morelli: None declared, Edoardo Rosato: None declared, Valeria Riccieri: None declared


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