ABSTRACT
Peripheral blood osteopontin (OPN) and endostatin (END) levels were studied in 35 patients with adrenal cortex tumors and 10 patients with pheochromocytoma before unilateral adrenalectomy, as well as in 10 healthy subjects (controls). Thirty days after surgery, OPN and END were evaluated again in 16 patients with adrenal cortex tumors and 4 female patients with pheochromocytoma. Before surgery, OPN blood concentrations increased in the group of patients with adrenal cortex carcinomas as compared to controls (p < 0.001) and the group with Conn syndrome (p < 0.05); they did not change after surgery. Before adrenalectomy, OPN blood levels in pheochromocytoma patients were also lower than in Conn syndrome subjects (p < 0.05). After adrenalectomy, the normal concentrations of END decreased only in the group of patients with hormonally inactive cortical adenomas (p < 0.05). We were unable to demonstrate any relationships between removed tumor volumes and OPN or END blood levels.
Subject(s)
Adrenal Gland Neoplasms/blood , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Endostatins/blood , Osteopontin/blood , Adrenal Cortex Neoplasms/blood , Adrenal Cortex Neoplasms/surgery , Adult , Aged , Biomarkers/blood , Case-Control Studies , Female , Humans , Hyperaldosteronism/blood , Hyperaldosteronism/surgery , Male , Middle Aged , Pheochromocytoma/blood , Pheochromocytoma/surgery , Young AdultABSTRACT
OBJECTIVE: Bidirectional communication between the neuroendocrine and immune systems is now a subject of an intensive investigation. Growth hormone-releasing hormone (GHRH) is synthesized by the hypothalamus, but is present also in the immune cells. Some recent data indicate also an immunomodulatory role of the neuropeptide. The aim of the study was to examine the influence of GHRH(1-44)NH2 on interleukin-6 and interleukin-8 secretion from human peripheral blood mononuclear cells cultured in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation using Böyum technique and cultured in a humidified atmosphere of 5 % CO2 and 95 % O2 at 37 degrees C for 24 hours in the presence of lipopolysaccharide (LPS) at the concentration of 2 microg/ml and GHRH(1-44)NH2 (the final neuropeptide concentrations to be tested were 10(-12) to 10(-6) M). ELISA methods were used to measure IL-6 and IL-8 concentrations in the supernatants of cultured cells RESULTS: GHRH(1-44)NH2 influenced IL-6 secretion from cultured cells, but significant inhibition of IL-6 release was observed at 10-6 M (p < 0.001). The negative correlation between the GHRH concentration studied and the IL-6 level in the supernatants was found (r = -0.759; p < 0.001). GHRH had no influence on the secretion of IL-8 from activated PBMC. CONCLUSIONS: Our results demonstrate that GHRH in vitro modulates IL-6 secretion from the human peripheral blood mononuclear cells, without any significant effect on IL-8 secretion.
Subject(s)
Growth Hormone-Releasing Hormone/pharmacology , Interleukin-6/metabolism , Interleukin-8/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/physiology , Adult , Cells, Cultured , Humans , Lipopolysaccharides/pharmacologyABSTRACT
Numerous reports indicate close interactions between the neuroendocrine and the immune systems. Hypothalamic neuropeptide, growth hormone-releasing hormone (GHRH) stimulates growth hormone (GH) secretion from the anterior pituitary gland, but recently some immunomodulatory properties of this peptide have also been demonstrated. In the present studies we evaluated the effect of human synthetic GHRH(1-44)NH(2) and GHRH antagonist (MZ-4-71) on interferon (IFN)-gamma secretion from human peripheral blood mononuclear cells (PBMC). GHRH(1-44)NH(2) at 10(-10), 10(-8) and 10(-6) M concentrations significantly (p < 0.05) increased the IFN-gamma level in supernatants of cultured cells, as compared with the controls. GHRH antagonist (MZ-4-71) at 10(-10), 10(-8) and 10(-6) M concentrations diminished the IFN-gamma level in supernatants in a dose-dependent manner, but statistically significant differences were observed only at 10(-8) M and 10(-6) M (p < 0.05 vs controls). Our results demonstrate that GHRH and GHRH antagonist MZ-4-71 can modulate IFN-gamma secretion in vitro by human peripheral blood mononuclear cells.
Subject(s)
Growth Hormone-Releasing Hormone/antagonists & inhibitors , Growth Hormone-Releasing Hormone/pharmacology , Interferon-gamma/biosynthesis , Monocytes/metabolism , Sermorelin/analogs & derivatives , Sermorelin/pharmacology , Adult , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Lipopolysaccharides/pharmacology , Male , Monocytes/drug effectsABSTRACT
Angiogenesis plays a key role in solid tumor formation, invasiveness and metastasis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is necessary in the process of neovascularisation. Antagonists of growth hormone-releasing hormone (GH-RH) have been shown to suppress both in vivo and in vitro growth and metastasis of many human cancer cell lines. The mechanisms that mediate the antitumorigenic actions of these antagonists involve direct and indirect pathways, but are not completely elucidated. We have examined the effect of GH-RH antagonist MZ-4-71 on proliferation activity and VEGF release from cultured murine endothelial cells HECa10 in vitro. MZ-4-71 at 10(-8) to 10(-6) M concentrations inhibited the proliferative activity of cultured cells and suppressed the release of VEGF into supernatants of 72 h endothelial cell cultures. To our knowledge this is the first study reporting antiangiogenic properties of GH-RH antagonists.
Subject(s)
Endothelial Growth Factors/metabolism , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Growth Hormone-Releasing Hormone/antagonists & inhibitors , Hormone Antagonists/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Lymphokines/metabolism , Sermorelin/analogs & derivatives , Sermorelin/pharmacology , Animals , Cell Division/drug effects , Cell Line , Cell Separation , Depression, Chemical , Endothelium, Vascular/drug effects , Mice , Trypsin/chemistry , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
Macroamylasaemia was produced in vitro by incubation of hydroxyethylstarch with serum, and in vivo by intravenous infusion of hydroxyethylstarch. Gel filtration on Sephadex G-100 revealed distinct differences in molecular size distribution between such hydroxyethylstarch-induced macroamylase and the usual form of naturally occurring macroamylase which was observed in a few patients from our hospital. Further studies demonstrated that the gel filtration elution pattern of amylase activity in serum containing hydroxyethylstarch-induced macroamylase is significantly altered with time in vitro and in vivo, probably because of an enzymatic degradation of the hydroxyethylstarch components of the macromolecular complexes. In a healthy volunteer the serum amylase activity was elevated to a maximum of 797 u/l and the renal clearance rate of amylase was diminished to a minimum of 0.3 ml/min after infusion of 500 ml of a 6% solution of hydroxyethylstarch, as compared to 300 u/l, and 0.95 ml/min, respectively, during the pre-infusion period.
