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A del Rey

Publications and source records attributed to A del Rey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Metabolic and endocrine effects of interleukin-1 in obese, diabetic Zucker fa/fa rats.

IL-1, a cytokine produced predominantly by cell from the macrophage lineage, can affect multiple neuroendocrine and metabolic functions. We report here effects of this cytokine in obese, diabetic Zucker fa/fa rats. These animals are modestly hyperglycemic, hyper-lipemic, and markedly hyperinsulinemic. Changes in the levels of glucose, lactate, triglycerides, free fatty acids, insulin, glucagon, and corticosterone were detected following a single intraperitoneal or intravenous injection of IL-1 into fa/fa rats. No comparable changes were observed following administration of insulin. In fa/fa rats, the diabetic status is particularly manifested by an abnormal glucose tolerance. Administration of a bolus injection of IL-1 normalized the response of diabetic fa/fa rats to a glucose load. These rats not only returned to their basal glucose levels quicker, but reached glucose concentrations in blood which were comparable to, or even lower than those of Fa/? rats. Although the mechanism underlying the effects of IL-1 in fa/fa rats are presently not clear, the results obtained suggest that this cytokine tends to normalize glucose homeostasis and stimulate fat mobilization in these animals.

Animals↗
PubMed1992

Interleukin-1 stimulates aldosterone secretion: involvement of renin, ACTH, and prostaglandins.

Interleukin-1 (IL-1), a cytokine produced during infection and inflammation, mediates some of the endocrinological alterations that parallel these processes. The purpose of this study was to determine whether human recombinant IL-1 (hrIL-1) affects aldosterone output as well as renin and adrenocorticotropic hormone (ACTH) release, two key factors in the regulation of mineralocorticoid secretion. We observed that intravenous administration of hrIL-1 into conscious unrestrained rats elicited a marked and rapid rise in aldosterone plasma levels in a dose-dependent manner. The hrIL-1-induced increase in aldosterone levels was associated with enhanced renin activity and increased ACTH levels in plasma. Furthermore, aldosterone levels of IL-1-injected rats were positively correlated with plasma renin activity (PRA), suggesting that the renin-angiotensin system contributes to the changes observed in the levels of the mineralocorticoid hormone. ACTH seems also to be implicated in the aldosterone response to hrIL-1 because the profile of the kinetic curves of changes in the levels of the pituitary hormone and aldosterone was similar. Pretreatment with the cyclooxygenase inhibitor indomethacin markedly reduced the increase in aldosterone plasma levels and PRA induced by IL-1, indicating that prostaglandins are involved in these effects of the cytokine. These results suggest that IL-1 may play an important role in the control of homeostasis during infectious and inflammatory diseases.

Adrenocorticotropic Hormone↗
PubMed1992

Immune-neuroendocrine circuits: integrative role of cytokines.

Several efficient autoregulatory mechanisms confer a certain degree of autonomy to the immune system. However, increasing evidence shows that immune processes operate in a coordinated fashion with other body systems. In this article, we discuss concepts and facts concerning interactions between immune and neuroendocrine mechanisms. There are clear examples that immune cells can be influenced by hormones, neurotransmitters, and neuropeptides and also by alterations in brain functions. Conversely, immune-derived products such as lymphokines and monokines can affect endocrine, autonomic, and central mechanisms. Neuroendocrine responses occur during the activation of the immune system. These responses can be elicited by innocuous antigens; they can also be detected during pathological conditions involving immune activation, and in many cases are dissociable from the effects of the disease itself and from the stress of being sick. On this basis, we emphasize the multidirectional nature of the communication processes between the immune, endocrine, and nervous systems. The role of lymphokines and monokines as messengers able to convey information to neuro and endocrine structures about the present state of activity of the immune system is stressed. The relevance of immune-neuroendocrine interactions for immunoregulation and host defenses is discussed as well as the active role of the immune system in mediating metabolic and homeostatic adjustments or derangements during the course of certain infectious, inflammatory, and neoplastic processes. The evidence available suggests that complex immune-neuroendocrine networks operate under both physiological and pathological conditions.

Animals↗
PubMed1991

On the mechanism of antiinflammation induced by tumor transplantation, surgery, and irritant injection.

Tumor transplantation, major surgery, and injection of nonspecific irritants elicit inflammation locally while suppressing inflammation induced subsequently and at distant sites. Such systemic antiinflammation in rodents occurs via corticosterone-independent and -dependent pathways. Based upon hormone measurements and the response to adrenalectomy, antiinflammation induced by irritants and certain surgical procedures is corticosterone independent while that which follows tumor transplantation is corticosterone dependent. However, injection of tumorous ascites stimulates both pathways since it contains two antiinflammatory factors: Factor A (molecular weight less than 2,000) does not alter hormone balance while Factor B (molecular weight 30,000-100,000) increases corticosterone levels and is corticosterone dependent. Desensitization of systemic antiinflammation develops rapidly regardless of whether it is corticosterone dependent (Factor B) or independent (Factor A or irritants). However, tumor transplantation resists desensitization possibly by inducing an immune response since lymphocytic mitogens prevent development of and break established desensitization. Nevertheless, abolition of tumor-induced antiinflammation follows injection of tumorous ascites by a mechanism that involves Factor B suppression of the corticosterone response to the tumor while Factor A apparently raises the threshold at which physiological increases in corticosterone inhibit leukocyte emigration. We conclude that systemic antiinflammation is a general consequence of a localized inflammatory reaction and that desensitization of such antiinflammation develops rapidly. Recent evidence indicates that certain mediators of inflammation are proinflammatory when administered intradermally but antiinflammatory when given intravenously. Thus, systemic antiinflammation may arise when chemical mediators of inflammation generated by a local reaction gain access to the circulation.

Adrenalectomy↗
PubMed1991

Cytokines as modulators of the hypothalamus-pituitary-adrenal axis.

The hypothalamus-pituitary-adrenal (HPA) axis is stimulated during the course of certain immune, inflammatory and neoplastic processes. IL-1 is an important immunologically derived cytokine mediating the stimulation of this axis, although not the only one. We have compared the relative potencies of the cytokines IL-1, IL-6 and tumor necrosis factor (TNF), which share several biological actions, for stimulating ACTH and corticosterone output in freely-moving rats. Although all three cytokines can stimulate the HPA axis, IL-1 was the most potent. This effect of IL-1 was also present during the neonatal period, when the response of the HPA axis to acute stress is reduced in rodents. The results support the existence of an immune-HPA axis circuit. The biological and clinical relevance of this circuit is discussed.

Adrenocorticotropic Hormone↗
PubMed1991

Feed-back interactions between immunological cells and the hypothalamus-pituitary-adrenal axis.

There is now increasing evidence that complex networks of interactions between immunological cells and endocrine, autonomic and brain structures operate during physiological and pathological conditions. Such interactions imply the existence of afferent messengers derived from the immune system, such as lymphokines and monokines, capable of integrating immune-neuroendocrine circuits. The operation of a glucocorticoid-associated immunoregulatory circuit is discussed as an example of these interactions. Under basal conditions, in non-overtly immunized animals, endogenous levels of glucocorticoids affect the number of immunoglobulin-secreting cells. At the time of the peak of the immune response to innocuous antigens, as well as following inoculation of infective agents, endotoxins or tumour cells, immunological cells release cytokines which can stimulate the pituitary-adrenal axis. The acute effect of these cytokines is mediated by stimulation of the release of corticotropin-releasing factor from the hypothalamus. Thus, immunological cells are not only influenced by glucocorticoids but their products can also control the activity of the hypothalamus-pituitary-adrenal axis. The possible relevance of these findings for immunoregulation and their implications for pathology are discussed.

Feedback↗
PubMed1989

Mechanism of virus-induced stimulation of the hypothalamus-pituitary-adrenal axis.

Increased blood levels of glucocorticoids are observed during certain viral infections. In this paper, we report data obtained from a model in rodents showing that the pituitary-adrenal axis is stimulated following inoculation of Newcastle Disease Virus (NDV). No evidence for an ectopic, lymphoid source of ACTH-like immunoreactive material capable of inducing this effect was obtained. Administration of virus-free supernatants from cocultures of human peripheral blood leukocytes with NDV also stimulated ACTH and glucocorticoid output in normal mice. This observation showed the immunological cell origin of the mediator of the hormonal effect. Pretreatment of the supernatant with anti-IL-1 sera neutralized its capacity to induce an increase in glucocorticoid and ACTH levels in blood. Furthermore, injection of IL-1 in nanogram amounts also increased ACTH and glucocorticoid blood levels. Thus, we conclude that IL-1 is the most likely mediator of the stimulation of the pituitary-adrenal axis during viral infection. The reported data are also discussed in the general context of the postulated glucocorticoid-associated immunoregulatory circuit.

Adrenocorticotropic Hormone↗
PubMed1989

Antidiabetic effects of interleukin 1.

Interleukin 1 (IL-1), a cytokine released mainly by activated macrophages-monocytes, affects glucose homeostasis and may mediate some of the metabolic derangements observed during certain inflammatory and infectious processes. In this report, it is shown that IL-1 acts as a hypoglycemic agent not only in normal animals but also in mice at early stages of alloxan-induced diabetes and in genetically diabetic, insulin-resistant C57BL/Ks db/db mice and C57BL/6J ob/ob mice. In these animal models, a single injection of a low dose of human recombinant IL-1 normalized glucose blood levels for several hours. This effect was not mediated by possible insulin secretagogue actions of the cytokine. Furthermore, IL-1 markedly reduced the levels of triglycerides in blood of streptozotocin-induced diabetic mice at later stages of the disease. Although the final mechanism of action is at present unknown, the results showed that IL-1 is a hormone with powerful antidiabetic properties. Defective production of this cytokine associated with diabetes could contribute to aggravate the course of the disease during infectious and inflammatory processes.

Animals↗
PubMed1989

Interleukin-1 and glucose homeostasis: an example of the biological relevance of immune-neuroendocrine interactions.

Interleukin-1 (IL-1), a cytokine mainly produced by monocytes-macrophages, plays a crucial role in immunological and inflammatory processes. We have recently demonstrated that IL-1 can also affect neuroendocrine mechanisms. In this paper, we refer to the capacity of IL-1 to affect glucose homeostasis. In normal mice, low doses of IL-1 induce a long-lasting hypoglycemia which is not dependent on possible insulin-secretagogue actions of this cytokine. The hypoglycemic effect of IL-1 is also observed in insulin-resistant diabetic mice. Furthermore, IL-1 seems to adjust the 'set point' for glucose regulation to a lower level. The effects of IL-1 on glucose homeostasis constitute a clear example of the biological relevance of immune-neuroendocrine interactions.

Animals↗
PubMed1989

Host endocrine responses during tumor growth.

Transplantation of the EL-4 lymphoma to syngeneic recipients caused significant endocrine changes which occurred very early as well as late after transplantation. Among the hormonal changes induced were a biphasic increase in the level of serum corticosterone, a biphasic decrease in serum insulin levels, an early decrease in prolactin and a terminal severe deficiency in thyroxine. The mechanism by which corticosterone levels are increased immediately following tumor transplantation appears to involve post-thymic T cells. In addition, the corticosterone response after tumor transplantation seems to be restricted to syngeneic recipients and does not seem to occur with allogeneic tumor transplantation. Further, the phenomenon may require an immunogenic tumor since the relatively nonimmunogenic mammary tumor virus (MTV) induced adenocarcinoma did not increase corticosterone in syngeneic C3H/He mice. Such data are consistent with the proposition that recognition of tumor antigen by mature T cells occurs within hours of tumor transplantation. This recognition appears to be MHC restricted. Whereas mitogen stimulation of T cells produces a glucocorticoid increasing factor designated GIF (Besedovsky et al., 1985b), it is reasonable to suggest that GIF is produced in vivo as part of the T cell response to tumor antigen. GIF in turn stimulates hypophyseal release of ACTH with a subsequent release of corticosterone from the adrenal gland. The biological relevance of this physiological increase in serum levels of corticosterone was examined with respect to the anti-inflammatory phenomenon often observed after tumor transplantation. First, a concordance was noted following tumor transplantation between elevated corticosterone levels and anti-inflammation. Similarly, transplantation of the MTV induced mammary adenocarcinoma which failed to increase serum levels of corticosterone did not exhibit anti-inflammation. Consistent with the concept that corticosterone levels increase following T cell recognition of tumor antigens, it is known that anti-inflammation does not occur with weakly immunogenic tumors but does follow transplantation of moderately immunogenic tumors (Normann, 1985b; Normann et al., 1985a). Second, adrenalectomy prevented the corticosterone response to tumor transplantation and eliminated tumor associated anti-inflammation. Additional studies are necessary to determine if the increase in serum levels of corticosterone alters other parameters of the host response to tumors. Anti-inflammation was shown to occur following tumor transplantation via a corticosterone dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Hormonal changes following tumor transplantation: factors increasing corticosterone and the relationship of corticosterone to tumor-induced anti-inflammation.

EL-4 lymphoma cells transplanted to syngeneic C57BL/6J mice induced a biphasic decrease in inflammation and a bi-phasic increase in serum levels of corticosterone. In addition, this tumor altered serum levels of 3 other hormones, resulting in a biphasic decrease in insulin, an early decrease in prolactin, and a terminal severe deficiency in thyroxine. Early changes occurred 16 to 48 hr after tumor transplantation and were of variable duration, while late-phase defects developed during the last few days of life. Soluble factors associated with tumor growth may mediate certain hormonal changes since serum levels of corticosterone increased and insulin decreased following injection of tumorous ascites into normal mice. Further, injection of cell-free tumor culture supernatants increased corticosterone levels. Hormonal changes following injection of soluble factors occurred after a delay of 16 hr indicating that the factors acted indirectly. Surgical adrenalectomy blocked the corticosterone increase induced by tumor transplantation or ascites injection and eliminated the anti-inflammatory effect of tumor transplantation while significantly decreasing the effect associated with injection of tumorous ascites. Thus, the physiologically induced increase in serum levels of corticosterone reached anti-inflammatory levels. Further, elevated levels of corticosterone are a major contributing factor to anti-inflammation induced by tumorous ascites injection and constitute the principal mechanism of anti-inflammation following tumor transplantation.

Animals↗
PubMed1988

Interleukin-1 induces changes in norepinephrine metabolism in the rat brain.

Interleukin-1 (IL-1) is a hormone that, apart from playing a key role in immune and inflammatory processes, can also affect mechanisms under brain control. To gain a better understanding of the action of this cytokine on the CNS, its effects on the contents of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their main metabolites and precursors, were evaluated in different regions of the forebrain, brain stem, and spinal cord. Following administration of human recombinant IL-1 (beta form) to rats, a modest decrease in the content of NE was observed in the hypothalamus as well as in the dorsal posterior brain stem. However, the most relevant finding was that 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the main NE metabolite, and the relation MHPG/NE were increased in all the regions studied, revealing a stimulatory effect of IL-1 on NE metabolism in the CNS. This effect seems to be specific for NE since no comparable changes in the brain content of DA, 5-HT, or its metabolite, 5-hydroxyindole acetic acid, were detected after administration of the cytokine. However, tryptophan was significantly increased in all brain regions and in the cervical spinal cord. The capacity of IL-1 to affect the metabolism of NE, a neurotransmitter involved in the control of a variety of brain functions, provides further proof for the relevance of this cytokine in brain-immune interactions.

Animals↗
PubMed1987

Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1.

Intraperitoneal administration of human recombinant interleukin-1 (IL-1) to rats can increase blood levels of corticosterone and adrenocorticotropic hormone (ACTH). The route by which IL-1 affects pituitary-adrenal activity is unknown. That the IL-1-induced pituitary-adrenal activation involves an increased secretion of corticotropin-releasing factor (CRF) is indicated by three lines of evidence. First, immunoneutralization of CRF markedly attenuated the IL-1-induced increase of ACTH blood levels. Second, after blockade of fast axonal transport in hypothalamic neurons by colchicine, IL-1 administration decreased the CRF immunostaining in the median eminence, indicating an enhanced release of CRF in response to IL-1. Third, IL-1 did not stimulate ACTH release from primary cultures of anterior pituitary cells. These data further support the notion of the existence of an immunoregulatory feedback circuit between the immune system and the brain.

Adrenal Glands↗
PubMed1987

Neuroendocrine and metabolic responses induced by interleukin-1.

We have previously demonstrated that Interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes, stimulates the pituitary-adrenal axis and affects glucose homeostasis. Comparative studies revealed that a beta form of recombinant human IL-1, similar to the mature peptide secreted naturally, is more powerful than other preparations of this monokine in stimulating adrenocorticotrophic hormone (ACTH) and corticosterone output. Another monokine, tumor necrosis factor (TNF), does not share with IL-1 the capacity to induce such effects. In extending our studies to rats, we showed that increased ACTH and blood corticosterone levels are also induced by IL-1 in this species. Another in vivo activity of IL-1 relates to its capacity to induce a reduction in blood glucose levels. Our studies strongly suggest that, as opposed to other effects elicited by IL-1, blockade of prostaglandin synthesis does not affect the capacity of IL-1 to stimulate insulin output and produce hypoglycemia. Administration of IL-1 to adrenalectomized mice, which are defective in counterregulatory mechanisms of glucose homeostasis, resulted in marked hypoglycemia. In contrast to the response observed in normal mice, in adrenalectomized animals this effect was paralleled by decreased blood insulin levels. IL-1 was also injected into alloxan-diabetic mice. A marked reduction in blood glucose levels occurred in these animals. This effect was already noticeable 1 hr after injection. After 2 hr and for at least another 6 hr, glucose levels of alloxan-treated mice injected with IL-1 remained within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

T lymphocytes affect the development of sympathetic innervation of mouse spleen.

We investigated whether the development of sympathetic innervation of the spleen is affected by lymphoid cells. Splenic noradrenaline (NA) levels of athymic nude mice (nu/nu) and normal thymus-bearing littermates (nu/+) were determined at different times during ontogeny. While no differences were detected at birth, higher splenic NA levels were found in 7-, 11-, and 21-day-old athymic mice. Thymus transplantation or thymocyte injection to newborn nude mice resulted in splenic NA levels comparable to those of normal nu/+ mice. Histochemical studies fully confirmed such differences. Taken together with previous studies, these results suggest that T lymphocytes or their products exert an inhibitory influence on sympathetic nerve fibers, thus leading to decreased NA content in the spleen. The data also illustrate the capacity of a nonneuronal cell in a peripheral organ to affect the process of autonomic innervation of this organ.

Aging↗
PubMed1987

Interleukin 1 affects glucose homeostasis.

Alterations in glucose metabolism are known to occur during certain types of inflammation and infectious diseases. Interleukin 1 (IL 1), an immune-derived cytokine released during these processes, is proposed to function as a mediator of such alterations, since administration of low subpyrogenic doses of human rIL 1 to mice and rats produced hypoglycemia. In mice this effect was paralleled by increased insulin, glucagon, and corticosterone blood levels. When IL 1 was repeatedly injected, mice remained hypoglycemic for at least 14 h after the last injection. Furthermore, these animals responded normally to a challenge with glucose, thus suggesting that the proper function of the pancreas was preserved. A moderate hypoglycemia, paralleled by increased glucagon and corticosterone blood levels, was also observed in IL 1-injected rats, but no increase in insulin levels was detected. IL 1 administration to adrenalectomized rats resulted in a more marked hypoglycemia and in a profound hypoinsulinemia. The results suggest that IL 1 causes hypoglycemia by increasing insulin blood levels and probably also by mechanisms independent of the insulin secretagogue action of this cytokine.

Adrenalectomy↗