Biomedical subjects

E Arzt

Publications and source records attributed to E Arzt.

66 records · Page 4Linked to original sources

PubMed1992

Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures.

The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells.

Adenoma↗

PubMed1992

Inhibition of interferon gamma production by peripheral blood mononuclear leukocytes of patients with sarcoidosis. Pathogenic implications.

Interferon gamma (IFN-gamma) production by stimulated peripheral mononuclear leukocytes of 30 patients with sarcoidosis was studied. A significant inhibition (64 percent, 5 to 330 IU/ml vs normal individuals = 1,000 +/- 250 IU/ml) in the IFN-gamma synthesis was found. The inhibition is due to a defect in the circulating monocytes and not in the peripheral T lymphocytes of these patients. This defect in the peripheral IFN-gamma production could be involved in the pathogenesis of this disease.

Biological Assay↗

PubMed1992

The inhibitory effect of the muscarinic agonist pilocarpine on lymphocyte activation involves the IL-2 pathway and the increase in suppressor cell function.

The inhibition of lymphocyte DNA synthesis by the cholinergic muscarinic agonist pilocarpine (5 x 10(-4) M) was not reversed by addition of exogenous recombinant Interleukin-2 (100-1000 IU/ml). Pilocarpine did not inhibit Interleukin-2 (IL-2) production by human peripheral blood mononuclear cells but decreased the number of interleukin-2 receptor bearing cells (TAC positive cells). Furthermore, pilocarpine increased the CD8:CD4 T lymphocyte ratio enhancing the suppressor cell function. All these effects were blocked by the muscarinic antagonist atropine (1 x 10(-6) M). As described for the specific lymphocyte nicotinic stimulation, the pure cholinergic muscarinic stimulation inhibits lymphocyte proliferation by enhancing suppressor activity.

Brain↗

PubMed1991

Lesions of the medial septal nucleus produce a long-lasting inhibition of T lymphocyte proliferation.

The influence of the central cholinergic system on the immune system was studied in Wistar rats by lesioning the medial septal nucleus. This lesion inhibited T cell proliferation of splenocytes and thymocytes induced by the mitogens concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) up to 25 days and did not affect proliferation at 40 days after lesioning. In contrast, the response to the B cell mitogen lipopolysaccharide from E. coli (LPS) was not affected at any time. These findings suggest a regulatory role of the cholinergic medial septal nucleus on T lymphocyte proliferation.

Animals↗

PubMed1991

Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes.

Serotonin inhibited in a concentration dependent way (10(-3) M to 10(-10) M) the LPS induced Tumor Necrosis Factor-alpha synthesis both, when added to the monocyte cultures from the beginning and when added together with the activating stimulus 8 hours before the end of the culture. The inhibitory effect was specifically blocked by the 5-HT1 and 5-HT2 serotonin antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. This indicates that only the 5-HT2 receptor family (5-HT2 or 5-HT1C) may be involved in the inhibitory effect. Serotonin seems to play an important immunomodulatory role in macrophage functions.

Humans↗

PubMed1990

Alpha-interferon induces cortisol release by human adrenals in vitro.

It is at present not clear whether alpha interferon (INF-alpha) can participate in the control of glucocorticoid blood levels through direct action on the adrenal gland. In this study, the possible action of INF-alpha on cortisol release by adrenal tissue was tested in vitro. Slices of normal human adrenals were incubated with INF-alpha for 3 h at 37 degrees C in 95% air and 5% CO2. Cortisol release by adrenal tissue was stimulated by INF-alpha, showing a dose-response curve from 20 IU/ml, the lowest dose that gave a response, to a maximal dose of 60 IU/ml when the response reached a plateau. The effect of INF-alpha on cortisol liberation by adrenal tissue in vitro may be implied in neuroimmune regulatory interactions.

Adrenal Glands↗

PubMed1987

Formation of ion-translocating oligomers by nigericin.

At pH 4.0, greater than 10(-7) M nigericin was found capable of conducting net charge transfer across bimolecular lecithin membranes, with a stoichiometry of three uncharged ionophore moieties per cation. At neutral or alkaline pH, nigericin catalyzed the transfer of net charge through dimer forms. In agreement with these results, quantitative analysis of nigericin-potassium complexes formed at pH 4.0 showed a 3:1 ratio, and a 2:1 ratio at neutral or alkaline pH. A 1:1 stoichiometry was observed when the ionophore complex was not transferred from methanol-water to chloroform. Moreover, 1H-NMR spectra of nigericin-cation complexes formed at pH 4.0, displayed clear-cut chemical shift variations different to those observed at neutral or alkaline pH. Thus, it is apparent that acid pH causes a transition from dimeric to trimeric forms of nigericin-cation complexes. The membrane conductance increased up to ten times when negatively charged phosphatidyl glycerol was used, while the conductance decreased in positively charged cetylpyridinium containing membranes at pH 4.0. These results suggest that the nigericin-K+ oligomeric complex is positively charged. In this respect, pKa values around 8.0 were obtained for the nigericin carboxylate group in media of different dielectric constant, indicating that this chemical group is undissociated under these conditions. Moreover, the values for the complex formation constants as well as the delta G values calculated for the dimers and trimers indicated that such ionophore cation oligomeric complexes are thermodynamically stable.

Anti-Bacterial Agents↗

PubMedDate not supplied

Glucocorticoids modulate soluble interleukin-2 receptor levels in vivo depending on the state of immune activation and the duration of glucocorticoid exposure.

We have studied the modulation of circulating soluble interleukin-2 receptor (sIL-2R) levels by glucocorticoids in subjects with different states of immune activation. In contrast to normal subjects, 40 mg methylprednisolone administration over 6 days resulted in a significant fall of elevated circulating sIL-2R levels (p < 0.05) in patients with active atopic dermatitis, most pronounced in those patients showing the highest pre-treatment levels of sIL-2R and scores of disease activity. Following administration of 1 mg dexamethasone, sIL-2R levels remained unchanged both in normal subjects and patients with atopic dermatitis. Circulating sIL-2R levels were significantly decreased in patients with long-term hypercortisolism due to Cushing's disease (p < 0.05) and significantly elevated (p < 0.05) in hypocortisolemic patients. Blockade of adrenal cortisol secretion by 1.5 g metyrapone did not change sIL-2R levels in normal subjects and sIL-2R levels were not affected in depressive patients, either before or after clinical remission or following 1.5 g metyrapone administration. These data suggest that the effect of glucocorticoid administration on circulating sIL-2R levels depends on the state of immune activation and the duration of glucocorticoid exposure. The circulating sIL-2R levels show significant changes in patients with chronic alterations of endogenous glucocorticoid secretion and in response to prolonged glucocorticoid therapy in disorders with immune activation.

Addison Disease↗

PubMedDate not supplied

Immunoneuroendocrine connectivity: the paradigm of the thymus-hypothalamus/pituitary axis.

It is now largely established that the immune and neuroendocrine systems cross-talk by using similar ligands and receptors. In this context, the thymus-hypothalamus/pituitary axis can be regarded as a paradigm of connectivity in both normal and pathological conditions. For example, cytokines and thymic hormones modulate hypothalamic-pituitary functions: (a) interleukin (IL)-1 seems to upregulate the production of corticotropin-releasing factor and by adrenocorticotropin by hypothalamic neurons and pituitary cells, respectively; (b) thymulin enhances LH secretion. Conversely, a great deal of data strongly indicate that the hypothalamic-pituitary axis plays a role in the control of thymus physiology. Growth hormone (GH) for example, enhances thymulin secretion by thymic epithelial cells (TEC), both in vivo and in vitro, also increasing extracellular matrix-mediated TEC/thymocyte interactions. Additionally, gap junction-mediated cell coupling among TEC is upregulated by ACTH. In a second vein, it was shown that GH injections in aging mice increased total thymocyte numbers and the percentage of CD3-bearing cells, as well concanavalin-A mitogenic response and IL-6 production. In addition to mutual effects, thymus-pituitary similarities for cytokine and hormone production have been demonstrated. Cytokines such as IL-1, IL-2, IL-6, interferon-gamma, transforming growth factor-beta and others can be produced by hypothalamic and/or pituitary cells. Conversely, hormones including GH, PRL, LH, oxytocin, vasopressin and somatostatin can be produced intrathymically. Moreover, receptors for various cytokines and hormones are expressed in both the thymus and the hypothalamus/pituitary axis. Lastly, it is noteworthy that a thymus-pituitary connectivity can also be seen under pathological situations. In this regard, an altered HPA axis has been reported in AIDS, human falciparum malaria and murine rabies, that also show a severe thymic atrophy.

Animals↗

PubMedDate not supplied

Differential regulation of interleukin-1 receptor antagonist by proopiomelanocortin peptides adrenocorticotropic hormone and beta-endorphin.

We have previously described the regulation of interleukin-1 receptor antagonist (IL-1ra) protein secretion and expression by IL-1, glucocorticoids and corticotropin-releasing hormone in monocytes in culture. In the present work, we analyze the direct effect of adrenocorticotropic hormone (ACTH) and beta-endorphin on the expression and secretion of IL-1ra by human monocytes in culture. ACTH exerted a dose-dependent inhibitory effect on lipopolysaccharide (LPS)-induced IL-1ra production and mRNA expression. Basal IL-1ra levels were not affected by treatment with any ACTH dose. In contrast, on human monocytes, beta-endorphin at concentrations as low as 10 pg/ml produced an increase of basal IL-1ra protein secretion and mRNA expression, this effect being reverted by pretreatment with naloxone. No effect of beta-endorphin was observed either in IL-1ra mRNA expression or protein secretion when cells were treated with LPS. The different effects of ACTH and beta-endorphin could account for their differential contribution to the inflammatory response: while ACTH contributes to the glucocorticoid overall control of the inflammatory response, beta-endorphin exerts an inhibitory tone on the resting IL-1 system. Because IL-1ra is essential in setting the level of monocyte and inflammatory response its differential regulation by the HPA axis hormones contributes to regulating the IL-1/inflammatory temporal response.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Cytokines: autocrine and paracrine roles in the anterior pituitary.

In addition to their role as lymphocyte messengers, cytokines also act at the anterior pituitary gland as autocrine or paracrine regulators of anterior pituitary function. As a cellular and molecular basis for this latter role, receptors for interleukin (IL)-1, IL-2 and IL-6 have been demonstrated in the pituitary of several species, as the endogenous production of the homologous cytokines. Additional cytokines are synthesized in or alter the function of the pituitary. IL-1, IL-2 and IL-6 regulate not only the secretion of pituitary hormones, but also the growth and proliferation of pituitary cells. This latter action suggests that intrinsically produced cytokines play a role in the pathogenesis of pituitary adenomas. Cytokines thus constitute a complex autocrine or paracrine network that contributes to the regulation of anterior pituitary physiology and pathophysiology.

Animals↗

PubMedDate not supplied

Glucocorticoids inhibit the autoregulatory induction of interleukin-1 in monocytes after endotoxin stimulation.

Interleukin-1 (IL-1) is an important mediator in the mechanisms underlying the immune and inflammatory responses. It has pleiotropic effects in host defense and, when present in high concentrations, participates in the development of pathological processes. IL-1 is the most potent cytokine in the activation of the hypothalamic-pituitary-adrenal axis during infection and therefore leads to a glucocorticoid increase. Glucocorticoids in a feedback loop inhibit the production of IL-1 induced by endotoxin. IL-1 also induces its own synthesis. In this report, we examine the role of glucocorticoids in the regulation of IL-1 autoregulatory induction in human monocytes at the level of IL-1 protein production and mRNA accumulation. Using recombinant IL-1 receptor antagonist we established that endogenously produced IL-1 affects induction of IL-1beta protein by lipopolysaccharide (LPS) at the level of mRNA expression. The inhibition of LPS-stimulated IL-1beta production and mRNA expression by glucocorticoids (dexamethasone and cortisol) reaches the same level with glucocorticoids alone or in combination with rIL-1ra. IL-1beta mRNA induced by exogenously added IL-1beta was also inhibited by glucocorticoids. These results indicate that glucocorticoids inhibit the autoregulatory loop of IL-1 in LPS-stimulated monocytes and constitute a mechanism for controlling IL-1 feedback stimulation.

Cells, Cultured↗