Interleukin-4 Blood Concentrations in Early and Metastatic Human Solid Neoplasms

1997 ◽  
Vol 12 (2) ◽  
pp. 75-78 ◽  
Author(s):  
P. Lissoni ◽  
D. Merlini ◽  
D. Pirato ◽  
S. Meregalli

Blood levels of the immunosuppressive cytokines IL-6 and IL-10 are often abnormally high in patients with advanced cancer. However, since IL-6 and IL-10 may be produced by macrophages and TH2 cells, the evidence of abnormally high values of IL-6 and/or IL-10 may reflect hyperactivation either of the macrophage system or of TH2 cell functions. In contrast, IL-4 is almost completely produced by the TH2 lymphocytes. Therefore, evaluation of IL-4 levels could help to differentiate macrophage from TH2 cell hyperactivation. This study was performed to investigate IL-4 serum levels in a group of cancer patients in relation to the stage of disease and to the secretion of other cytokines. The study included 50 patients, 28 of whom showed distant organ metastases. Lung cancer and gastrointestinal cancers were the most frequent neoplasms in our patients. The control group consisted of 60 healthy subjects. IL-4 was measured by the Elisa method. No patient showed high levels of IL-4. No significant differences were seen between controls and cancer patients, nor between metastatic and non-metastatic patients. In addition, no significant differences in IL-4 mean values were found between patients with normal or high levels of IL-6 and IL-10, or between patients with normal or low IL-2 concentrations. This preliminary study seems to exclude cancer-related abnormally high secretion of IL-4. Therefore, the high levels of IL-6 and/or IL-10 often occurring in advanced neoplastic disease would mainly depend on macrophage production.

2019 ◽  
Vol 2 (1) ◽  
pp. 14-19
Author(s):  
Lissoni Paolo ◽  
◽  
Porro Giorgio ◽  
Cenaj Vezika ◽  
Aymerich Tiziana ◽  
...  

It is known that lymphocytopenia is one of the most negative biomarkers in cancer patients, being an expression of cancer-related immunosuppression. Today it is known that, despite its complexity, the antitumor immunity is mainly mediated by dendritic cell-T lymphocyte system and suppressed by the macrophage-regulatory T lymphocyte system. Then, lymphocyte-to-monocyte ratio (LMR) has been proven to represent a more appropriate prognostic clinical index than the simple lyphocytopenia alone. Because of the fundamental role of lymphocytes in mediating tumor cell destruction, the correction of cancer-related lymphocytopenia could influence the clinical history of the neoplastic disease. At present, the only cytokine able to induce a clear in vivo lymphocytosisis IL-2. However, it has been demonstrated that the immune system is physiologically under a neuroendocrine control, and that the pineal hormone MLT may stimulate T lymphocyte proliferation and activation. On these bases, we have evaluated the effect of highdose MLT therapy in metastatic solid tumor patients with persistent lymphocytopenia and abnormally low values of LMR. The study included 14 patients, and the results were compared to those found in a control group of 20 lymphocytopenic untreatable metastatic cancer patients treated with the only best supportive care alone. Patients received MLT at a dose of 100 mg/day orally in the evening for 3 consecutive months. Lymphocyte mean count increases on MLT therapy, and the values observed after two months of therapy were significantly higher than the pretreatment ones, with a normalization of lymphocyte number in 4/14 (29%) patients, whereas no spontaneous lymphocyte rise occurred in the control group. On the other hand, monocyte count rapidly diminished on MLT therapy, and LMR mean values observed after only one month of treatment was significantly higher than that found prior to therapy, whereas it significantly decreases in controls. This preliminary study shows that high-dose MLT may improve the immune status of cancer patients, and be effective in the treatment of disseminated cancer-related lymphocytopenia.


1988 ◽  
Vol 3 (3) ◽  
pp. 193-196 ◽  
Author(s):  
S. Barni ◽  
P. Lissoni ◽  
S. Crispino ◽  
F. Rovelli ◽  
G. Esposti ◽  
...  

Melatonin secretion is often enhanced in patients with cancer. In the light of a reported correlation between melatonin levels and body size, we investigated blood levels of this pineal hormone in a group of 72 patients affected by cancer, 30 of whom had body weight within the normal range, 30 were obese and the last 12 cases had body weight below the normal range, in order to establish whether in fact melatonin blood concentrations were related to body size. Melatonin levels were high in 19/72 patients (26%). The mean levels of the pineal hormone were similar in patients with normal, low and high body weight. Finally, there was no significant correlation between melatonin values and body weight, height or surface. Melatonin secretion thus does not appear to be influenced by body size in cancer patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
M. Sambucci ◽  
F. Laudisi ◽  
F. Novelli ◽  
E. Bennici ◽  
M. M. Rosado ◽  
...  

T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosy)lation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose) polymerases (PARPs). Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT) activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+cells as well as IFN-γproduction, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.


1982 ◽  
Vol 92 (2) ◽  
pp. 237-250 ◽  
Author(s):  
G. A. LINCOLN ◽  
O. F. X. ALMEIDA ◽  
H. KLANDORF ◽  
R. A. CUNNINGHAM

Eight adult Soay rams (four control and four cranially sympathectomized by removal of the superior cervical ganglia) were exposed to alternating 16-week periods of short days of 8 h light: 16 h darkness (8L : 16D) and long days (16L : 8D) for more than 3 years, and the changes in the diameter of the testes were recorded. Once during short days and once during long days blood samples were collected hourly for 28 h, and the concentrations of melatonin, prolactin, FSH, LH, testosterone, tri-iodothyronine (T3), thyroxine (T4) and cortisol were measured by radioimmunoassay. In the control rams the testes were reduced in size during long days compared to short days, and the blood concentrations (24-h mean values) of FSH, LH and testosterone were decreased. The levels of prolactin were much increased, while there was no significant change in the mean levels of melatonin, T3, T4 and cortisol. During both photoperiods there was considerable hour-to-hour variation in all eight hormones indicative of episodic secretion, as well as a consistent variation related to the time of day which was most pronounced for melatonin and T3. There was a clear difference in the daily profile of plasma melatonin levels between short and long days. In the superior cervical ganglionectomized rams there were no significant changes in the size of the testes or in the hormone titres between short and long days. Compared to the controls the plasma levels of LH, FSH, testosterone and prolactin were in the intermediate range. Some consistent diurnal variation was evident in the levels of all the hormones measured, with a pattern similar to the controls for a few of the hormones (e.g. T3) but quite different for others (e.g. melatonin).


1988 ◽  
Vol 3 (2) ◽  
pp. 82-86 ◽  
Author(s):  
S. Barni ◽  
P. Lissoni ◽  
S. Crispino ◽  
G. Cattaneo ◽  
F. Rovelli ◽  
...  

The pineal gland and opioid peptides play roles in the neuroendocrine control of immunity. Both neuroendocrine and immune dysfunctions have been observed in cancer but the importance of the altered secretion of neurohormones in the immunoincompetence of cancer patients has never been investigated. This study concomitantly evaluated neuroendocrine and immune functions in 40 patients with early or advanced neoplastic disease. In each patient, melatonin and β-endorphin blood levels and lymphocyte subtypes were determined on venous blood samples collected during the morning. Metastatic patients had lower melatonin levels and a lower T4/T8 ratio than patients without metastases but no significant correlation was found between melatonin and the T4/T8 ratio. β-endorphin levels appeared to be normal in all patients. These results suggest that melatonin and β-endorphin secretion have no role in determining immune dysfunctions in cancer.


1998 ◽  
Vol 13 (3) ◽  
pp. 169-171 ◽  
Author(s):  
P. Lissoni ◽  
F. Rovelli ◽  
M. Mandalà ◽  
S. Barni

In addition to the better known cytokines IL-2 and IL-12, IL-15, which is mainly produced by macrophages, is a new antitumor cytokine with a mechanism of action similar to that of IL-2. At present, however, there are no data about IL-15 secretion in cancer patients. This study was carried out to evaluate IL-15 blood concentrations in patients with early or advanced cancer and their possible variations in response to IL-2 cancer immunotherapy. The study included 40 patients with solid tumors, 24 of whom had metastatic disease. In addition, IL-15 secretion was evaluated during subcutaneous low-dose IL-2 therapy (6 million IU/day for 6 days/week for 4 weeks) in 14 metastatic renal cell cancer patients by collecting blood samples at weekly intervals. The control group consisted of 40 age-matched healthy subjects. Serum levels of IL-15 were measured by an enzyme immunoassay. No significant difference in mean serum levels of IL-15 was observed between cancer patients and controls. Moreover, the mean serum levels of IL-15 found in metastatic cancer patients were not significantly different from those found in patients with limited disease. Finally, no significant changes in mean levels of IL-15 occurred during IL-2 cancer immunotherapy. This preliminary study would suggest that IL-15 secretion is substantially within the normal range in cancer patients, both in early and advanced disease, and no variation seems to occur in response to IL-2 administration.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1829
Author(s):  
Silvio Buscemi ◽  
Carola Buscemi ◽  
Davide Corleo ◽  
Giovanni De Pergola ◽  
Rosalia Caldarella ◽  
...  

Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10–12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass–kg (r = −0.40; p < 0.05) and body mass index (r = −0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass–kg (r = −0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss.


2020 ◽  
Vol 6 (7) ◽  
pp. 133-138
Author(s):  
V. Malevannaya ◽  
E. Alymbaev ◽  
O. Atykanov

The study presents data on the examination of 100 children aged 7 to 14 years with a disturbance of the motor-evacuation function of the bile excreting system in the hypomotor type (57 children — I clinical group) and hypermotor type (43 children — II clinical group). As a control group, 20 somatically healthy children were examined. It was shown that with hypomotor dyskinesia of the gallbladder, the activity of the cytokine (interleukin) system in the blood plasma was significantly superior to activity in hypermotor dyskinesia. Combined therapy in children’s second clinical group leads to normalization of blood levels of interleukins, whereas the children of the first clinical group stored in elevated blood concentrations of interleukin closure during treatment.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14005-e14005
Author(s):  
Valeria A. Bandovkina ◽  
Elena M. Frantsiyants ◽  
Ayna M. Salatova ◽  
Dmitry A. Kharagezov ◽  
Oleg I. Kit

e14005 Background: Cutaneous melanoma (CM), breast cancer (BC) and lung cancer (LC) metastasize to the brain most frequently. Early diagnosis of cerebral metastases is challenging and requires new prognostic criteria. Imbalance of thyroid and glucocorticoid hormones changes the growth and development of malignant tumors. The purpose of the study was to identify readily available prognostic criteria for cerebral metastases in cancer patients at various stages of treatment and follow-up. Methods: Blood levels of cortisol and total triiodothyronine (tT3) were determined by RIA (Immunotech, Czech Republic) in patients with BC (n = 50), LC (n = 50) and CM (n = 50) without brain metastases and in patients with BC (n = 25), LC (n = 25) and CM (n = 25) with cerebral metastases. Results: Blood levels of cortisol in BC, LC and CM patients were normal in 63-84% and elevated on average by 1.7 times in 16-37%. Levels of tT3 in LC were normal, and in BC and CM – within the normal limits, but 1.3 times lower than the mean values. In patients with cerebral metastases, cortisol was lower than the norm by 4.9, 2.5 and 3.6 times in 36% BC, 75% LC and 45% CM cases, respectively. Levels of tT3 in all patients with cerebral metastases were lower than the norm or values in patients without metastases by 2 times and lower. Conclusions: Decreased levels of both cortisol and tT3 in patients with BC, LC and CM may serve as one of prognostic markers of possible development of cerebral metastases. The dynamic determination of levels of thyroid and glucocorticoid hormones is required in cancer patients at various stages of treatment and follow-up.


Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1443-1453 ◽  
Author(s):  
Helena Ahlfors ◽  
Amita Limaye ◽  
Laura L. Elo ◽  
Soile Tuomela ◽  
Mithila Burute ◽  
...  

Abstract Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation.


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