Circulating IL-6 and neopterin concentrations link cell-mediated immunity and tumor stage in patients with gastro-intestinal adenocarcinoma: relevance to the pituitary-adrenal axis and pituitary-thyroid axis

Pteridines ◽  
2016 ◽  
Vol 27 (1-2) ◽  
pp. 17-25
Author(s):  
Ayse Basak Engin ◽  
Atilla Engin ◽  
Aylin Sepici-Dincel ◽  
Osman Kurukahvecioglu

AbstractAlthough cortisol is a powerful modulator of the immune system and inhibits production of pro-inflammatory cytokines, adrenocorticotropic hormone (ACTH) levels do not correspond to the chronically elevated concentrations of cortisol in cancer patients. Thyroid stimulating hormone (TSH) has been shown to have an effect on immunological functions. Actually it is not known whether cortisol, TSH and IL-6 have an effect on tumor progression via modulation of cell mediated immunity in patients with gastrointestinal carcinoma. Sixty-seven gastrointestinal cancer patients and 42 cancer-free subjects with cholelithiasis as the control group, were included in the study. Serum ACTH, cortisol, TSH, thyroid hormones, IL-6, IL-10 and neopterin levels were measured. Diagnosis and pathological staging were confirmed by surgical intervention. Cortisol levels were correlated with IL-6 in cancer patients. In addition to elevated neopterin values, linear regression analysis revealed that serum neopterin was associated more strongly with the increase of cortisol rather than IL-6 levels in advanced stage carcinoma. Furthermore, neopterin also correlated with IL-6, IL-10, cortisol and TSH levels in advanced carcinoma cases. These data indicated that cortisol, IL-6 and neopterin values of cancer patients were influenced by the tumor presence and progression.

2021 ◽  
Vol 80 (3) ◽  
pp. 567-578 ◽  
Author(s):  
Rosaria Sciarrillo ◽  
Mariana Di Lorenzo ◽  
Salvatore Valiante ◽  
Luigi Rosati ◽  
Maria De Falco

Abstract Different environmental contaminants disturb the thyroid system at many levels. AlkylPhenols (APs), by-products of microbial degradation of AlkylPhenol Polyethoxylates (APEOs), constitute an important class of Endocrine Disrupting Chemicals (EDCs), the two most often used environmental APs being 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP). The purpose of the present study was to investigate the effects on the thyroid gland of the bioindicator Podarcis siculus of OP alone and in combination with NP. We used radioimmunoassay to determine their effects on plasma 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5,5′-L-thyroxine (T4), thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) levels in adult male lizards. We also investigated the impacts of AP treatments on hepatic 5′ORD (type II) deiodinase and hepatic content of T3 and T4. After OP and OP + NP administration, TRH levels increased, whereas TSH, T3, and T4 levels decreased. Lizards treated with OP and OP + NP had a higher concentration of T3 in the liver and 5′ORD (type II) activity, whereas T4 concentrations were lower than that observed in the control group. Moreover, histological examination showed that the volume of the thyroid follicles became smaller in treated lizards suggesting that that thyroid follicular epithelial cells were not functionally active following treatment. This data collectively suggest a severe interference with hypothalamus–pituitary–thyroid axis and a systemic imbalance of thyroid hormones. Graphic Abstract


1978 ◽  
Vol 56 (6) ◽  
pp. 950-955 ◽  
Author(s):  
J. H. Dussault ◽  
P. Walker

The effect of chronic propylthiouracil (PTU) and low iodide diet (LID) on the development of the hypothalamo–pituitary–thyroid axis in the rat has been studied. Pregnant and neonatal rats received 0.05% PTU in their drinking water or LID (distilled water and LID: Teklad Mills, Madison, Wisconsin). Control animals received tap water and Purina rat chow ad libitum. Hypothalamic thyrotropin-releasing hormone (TRH), pituitary and serum thyroid-stimulating hormone (THS), and serum thyroxine (T4) and triiodothyronine (T3) were measured by specific double-antibody radioimmunoassay. Both PTU- and LID-exposed animals had low hypothalamic TRH concentrations at 1 day and a rapid rise to peak levels of 2.4 ± 0.4 pg/μg protein (mean ± SEM) between 12 and 24 days in the PTU animals and 3.2 ± 0.4 pg/μg protein between 12 and 18 days in the LID rats. Hypothalamic TRH concentrations remained relatively stable in the PTU animals, whereas in the LID rats, after a brief but significant decline from 24 to 28 days, hypothalamic TRH concentrations rose to the highest values observed at 57 days (3.9 ± 0.5 pg/μg protein). Both groups of animals had elevated serum TSH levels at 1 day, with higher values seen in the PTU group (p < 0.01), and both showed a rapid rise at 12 days. Thereafter, serum TSH concentrations remained high in the PTU rats but declined to stable, albeit elevated, levels by 24 days (1260 ± 140 ng/ml) in the LID animals. Hypothyroidism was confirmed in the PTU animals by undetectable T4 and reduced T3 concentrations. In the LID rats, serum T4 concentrations rose from undetectable levels at 1 day to stable values by 32 days (2.18 ± 0.13 μg/dl). Serum T3 rose to peak values of 157.0 ± 6.9 ng/dl at 32 days and was elevated at all times after 12 days. These data suggest that chronic exposure to PTU or LID results in a marked derangement of the ontogenetic pattern of the hypothalamo–pituitary–thyroid axis. In addition, neonatal rats exposed to LID appear to respond appropriately by preferential T3 production.


2011 ◽  
Vol 6 (4) ◽  
pp. 518-523
Author(s):  
Negrin Negrev ◽  
Yuri Nyagolov ◽  
Margarita Stefanova ◽  
Emiliya Stancheva

AbstractEffects of the hormones of the hypothalamic-pituitary-thyroid axis on some basic parameters of the activity of protein C anticoagulation pathway in rats are studied. Thyrotropin-releasing hormone (0.06 mg/kg body mass), thyrotropin (1 IU/kg), triiodothyronine (T3) (0.08 mg/kg), thyroxine (T4) (0.08 mg/kg), administered subcutaneously for three consecutive days on four different groups of rats increased significantly activated protein C, free protein S and protein S activity, and reduced the soluble endothelial protein C receptor. Protein C antigen and total protein S were significantly elevated only by thyrotropin-releasing hormone and thyroid-stimulating hormone, but they were not affected by T3 and T4 treatment. The data indicate the hypothalamic-pituitary-thyroid axis is involved in the regulation of the protein C anticoagulation pathway in rats by activation of this system, suggesting a tendency of hypocoagulability.


2022 ◽  
Vol 12 ◽  
Author(s):  
David Tak Wai Lui ◽  
Chi Ho Lee ◽  
Wing Sun Chow ◽  
Alan Chun Hong Lee ◽  
Anthony Raymond Tam ◽  
...  

BackgroundBoth lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated.MethodsWe included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission.ResultsA total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p&lt;0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p&lt;0.001) and LYM (p&lt;0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend &lt;0.001).ConclusionTSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.


2014 ◽  
Vol 29 (1) ◽  
pp. e49-e54 ◽  
Author(s):  
Eran Sadot ◽  
Sarah Kraus ◽  
Michael Stein ◽  
Ilana Naboishchikov ◽  
Ohad Toledano ◽  
...  

Background The CD24 gene has been correlated with poor prognosis of various malignancies. The significance of CD24 in esophageal cancer remains unknown. Our aim was to evaluate the association between CD24 genetic polymorphism and esophageal cancer. Materials and Methods Between June 2011 and May 2012 patients with esophageal cancer and healthy controls were prospectively enrolled and clinicopathological data were collected. Genomic DNA was extracted and restriction fragment length polymorphism (RFLP) analysis was performed to determine CD24 polymorphism at the coding region of CD24, which results in a substitution of the amino acid Ala by Val. Statistical significance was determined by unpaired t-test, χ2-test, and Fisher's exact test. Results A total of 102 patients were included, of whom 51 had esophageal cancer and the rest comprised a healthy control group. The incidence of the polymorphism variant (Val/Val) among the healthy subjects and the esophageal cancer cohort was 6% in both groups. The incidence of N3 (metastasis in 7 or more regional lymph nodes) was markedly higher in those esophageal cancer patients who carried the polymorphism variant compared with those who did not carry it (66% and 2%, respectively, p=0.007). No significant difference was found between the groups with regard to age, gender, histology type, tumor location, tumor stage, and other histological characteristics of the tumor. Conclusions This CD24 polymorphism may serve as a novel prognostic marker identifying esophageal cancer patients with poor prognosis. Further studies are warranted to evaluate CD24 function and to validate its predictive potential with regard to esophageal cancer.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hye-Rim Kim ◽  
Young Hwa Jung ◽  
Chang Won Choi ◽  
Hye Rim Chung ◽  
Min-Jae Kang ◽  
...  

Abstract Background Thyroid hormones are critical for growth and brain development during the newborn period and infancy. Because of delayed maturation of the hypothalamic-pituitary-thyroid axis in preterm infants, thyroid dysfunction is common, and thyroid stimulating hormone (TSH) elevation is often delayed in preterm infants. The objective of this study was to determine the incidence of thyroid dysfunction requiring levothyroxine treatment and to identify its risk factors in preterm infants. Methods A retrospective cohort study was performed on preterm infants who were born before 32 gestational weeks and admitted to a single tertiary academic center for more than 8 weeks between January 2008 and December 2014. In these infants, serial thyroid function tests (TFTs) measuring serum TSH and free thyroxine (fT4) were routinely performed at 1, 3, and 6 weeks of postnatal age. Results Of the 220 preterm infants enrolled, 180 infants underwent TFTs at 1, 3, and 6 weeks of postnatal age and were included in the study. Of the 180 infants, 35 infants (19.4%) were started on levothyroxine treatment based on the results of serial TFTs. Among the 35 infants who were treated with levothyroxine, 16 infants (45.7%) had normal results on the initial TFT. Three of these 16 infants continued to have normal results on the second TFT. Thyroid dysfunction requiring levothyroxine treatment was significantly associated with maternal pregnancy-induced hypertension (adjusted odds ratio 2.64, 95% confidence interval 1.02–6.81). Conclusions Thyroid dysfunction requiring levothyroxine treatment occurred in nearly one-fifth of preterm infants born before 32 gestational weeks. Nearly half of the preterm infants who were treated with levothyroxine had normal TSH and fT4 levels at 1 week of postnatal age. The findings of the present study suggest that serial TFTs is important to find preterm infants who require levothyroxine treatment.


2018 ◽  
Vol 43 (4) ◽  
pp. 371-380
Author(s):  
Nagaraj Banavara Swarnalatha ◽  
Neena Roy ◽  
Mahesh Manjunath Gouda ◽  
Rajeish Moger ◽  
Asha Abraham

Given the association between subclinical hypothyroidism and metabolic syndrome, we wanted to explore if high-fat, simple-carbohydrate (HFSC) diet affects hypothalamus–pituitary–thyroid axis. One-month-old male C57BL/6J mice were fed with control (C) and HFSC (T) feed (n = 18 each), respectively, for 5 months. There was a significant increase in triiodothyronine in the T group (13.5%) compared with the age-matched C group by the fifth month. Thyroid-stimulating hormone was significantly higher (1 month: 1.9-fold; 3 months: 2.66-fold; 5 months: 3.5-fold) from the first to fifth months in the T group compared with age-matched C group. Thyrotropin-releasing hormone (TRH) gene expression showed significant decrease (1 month: 83.2%; 5 months: 40.7%) in the T group compared with the age-matched C group. TRHR1 showed significant decrease in the T group compared with the age-matched C group throughout the study (1 month: 82.8%; 3 months: 45.7%; 5 months: 75.2%). However, TRHR2 showed dynamic change during the study. Initially there was significant (1 month: 0.104-fold) downregulation, followed by significant upregulation (3 months: 3.6-fold) and downregulation (0.73-fold) by the fifth month in the T group compared with the age-matched C group. There was marked depletion of functional follicular cells and colloid substance in the thyroid glands of the T group by the fifth month compared with the C group. Leptin receptors ObRa (1 month: 48.25%; 5 months: 88%) and ObRb (1 month: 46.9%; 5 months: 63.3%) were significantly downregulated in the T group compared with the age-matched C group in the first and fifth months of feeding the respective diets. The expression of p-STAT3, a transcription factor known to have a role in energy balance, intermediate metabolism, and leptin signalling was seen to decrease significantly (6.25-fold) in the hypothalamus of the T group compared with the age-matched C group. In conclusion, HFSC feed disrupts the hypothalamus–pituitary–thyroid axis in male C57BL/6J mice.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15508-e15508
Author(s):  
Anastasia O. Sitkovskaya ◽  
Elena Yu. Zlatnik ◽  
Oleg I. Kit ◽  
Inna A. Novikova ◽  
Elena S. Bondarenko ◽  
...  

e15508 Background: The most important stages of metastatic cascade are extravasation and invasion of malignant cells and their surviving in blood. The vast majority of circulating tumor cells (CTC) is destroyed by immune cells. The role of immune system which is able to play not only antitumor but also prooncogenic role is manifested both on local and systemic levels. We studied correlations between lymphocyte subsets` content in blood and in tumor of colorectal cancer patients (II, III, IV stages) with and without CTC. Methods: 60 colorectal cancer patients with II (n = 20), III (n = 20) and IV (n = 20) stages underwent surgery without previous chemotherapy. CTC were measured in blood by CellSearchSystem™ (JanssenDiagnostics, LLC), cell-mediated immunity was assessed in blood by flow cytometry (BD Canto II) and in tissue after surgery by immunohistochemistry; some markers of proliferation and epithelial-mesenchimal transition (EMT) in tumor cells (Ki-67, E- and N-cadherins) were also studied. Criteria of CTC-positive and CTC-negative samples were > 3 and ≤3 respectively. Correlative analysis was performed between the data of the patients with and without CTC in each stage, r was counted. Results: In CTC-positive patients with all the stages the number of strong and moderate correlations between system immunologic factors involving CD8+ appeared to be fewer than in CTC-negative ones (7 vs 19). On the contrary, the number of correlations with T regs in CTC-positive was increased: 5 vs 3 in CTC-negative patients. In patients with CTC > 3 fewer correlations were noted between factors of local and systemic immunity than in CTC-negative ones (9 vs 4 in II stage) and total disruption of all the correlations between system immunologic factors and proliferating tumor cells in III and IV stages was established. Some pathologic correlations appeared in CTC-positive patients like moderate direct one between activated T-lymphocytes` amount and Ki-67+ tumor cells. The number of correlations between intratumoral lymphocytes and tumor cells expressing proliferation and EMT markers in CTC-positive patients was decreased in comparison with CTC-negative ones (4 vs 10 in II stage, 1 vs 9 in III, 2 vs 9 in IV stage). Conclusions: The presence of CTC in colorectal cancer patients rather than tumor stage is associated with imbalance of their systemic and local immunologic factors. This provides some evidence that disruption of interactions in the immune system is at least partly due to CTC.


2011 ◽  
Vol 11 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Gianluigi Mazzoccoli ◽  
Valerio Pazienza ◽  
Ada Piepoli ◽  
Lucia Anna Muscarella ◽  
Francesco Giuliani ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Florian Schmidt ◽  
Thomas Braunbeck

In the past, various approaches have been developed to detect adverse effects of pollutants on the thyroid of vertebrates, most of these with special emphasis on the South African clawed frog,Xenopus laevis. Although fish are primarily affected by thyroid-disrupting chemicals, studies into alterations of the thyroid of fish are scarce. Therefore, effects of the reference compound propylthiouracil on histopathology of the thyroid axis were analyzed in a modified early life-stage test with zebrafish (Danio rerio) exposed to propylthiouracil. The test substance induced dose-dependent alterations of thyroidal tissue concomitant with increases in the number of surrounding blood vessels. Despite this massive proliferation of the thyroid, zebrafish were not able to maintain thyroxin concentrations. The pituitary was affected displaying significant alterations in thyroid-stimulating hormone cell counts. Quantitative evaluation of pituitary surface areas revealed a dose-dependent increase of adenohypophyseal tissue. Distinct histopathological effects may contribute to a more easy identification and interpretation of alterations induced by thyroid-disrupting chemicals.


Sign in / Sign up

Export Citation Format

Share Document