摘要:

In this study, the effect of restraint stress on alterations in the immune cell distrubution was examined in bone marrow, liver, thymus, and spleen. In bone marrow, stress induced a striking increase in both the proportion and number of CD3+CD4+, CD3+CD8+, B220brightIgM+, CD3–IL-2Rβ+ and CD3intIL-2Rβ+ cells. Such an increase was partially reversed by pretreatment with RU-486, a steroid receptor antagonist, while it was profoundly enhanced by either sympathectomy with 6-hydroxydopamine hydrobromide or by a β-adrenergic blockade with propranolol, a β-adrenergic receptor antagonist; this suggests that corticosteroids and catecholamines may act in opposition with regard to such an immune-cell accumulation in bone marrow. In the liver, stress decreased the proportions of CD3intIL-2Rβ+, CD3–IL-2Rβ+, and B220brightIgM+ cells, while it increased the proportion of CD3brightIL-2Rβ– cells, thus demonstrating that different subpopulations were differentially affected. In the thymus and spleen, stress only slightly affected the proportions of lymphocyte subpopulations, although both tissues showed a drastic reduction in the number of lymphocytes. Taken together, these results suggest that restraint stress induces tissue-specific changes in the immune-cell

ISSN:1021-7401    

DOI:10.1159/000097329

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

It has been well documented that the medial parvocellular subnucleus of the hypothalamic paraventricular nucleus (PVN) participates in immune regulation by releasing corticotrophin-releasing hormone (CRH), which triggers the hypothalamus-pituitary-adrenal axis, leading to immunosuppression. Little is known about other possible influences of PVN on immunomodulation. Evidence, however, has been accumulating recently, indicating possible involvement of other subnuclei of this nucleus. By using the c-fos technique, the present study investigated the neuronal groups of the PVN that were activated in response to intracerebroventricularly administered IL-1β. In addition to strong Fos expression in the dorsal part of medial parvocellular subnucleus of the PVN, where CRH neurons are located, two more neuronal groups were found to express Fos protein. One of which was the oxytocin-immunoreactive magnocellular neurons, mainly concentrated in the anterior and medial mag-nocellular subnuclei of the PVN. The magnocellular PVN subnuclei are known to project to, and release their hormones, in the posterior pituitary. Another group of Fos-immunoreactive neurons were found in the brainstem and spinal cord projecting area of the PVN. By combining retrograde tracing technique and Fos immunohistochemistry, it was proved that many of the spinal cord projecting PVN neurons were activated following IL-1β administration, through which the spinal cord sympathetic outflow might be regulated. The present study indicates that the hypothalamic PVN may serve as an integrative center for immunomodulation via three channels, i.e., the CRH and oxytocin neuroendocrinological and the PVN-spinal cord sympathetic neural channel

ISSN:1021-7401    

DOI:10.1159/000097330

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Azido-3′-deoxy-thymidine (AZT) is a drug extensively used in the treatment of AIDS. AZT was incubated in vitro either with the pituitary-hypothalamus complex (PHc) or the intact pituitary (PI) of male rats. The PHc is comprised of the hypothalamus and the attached pituitary gland. After a preincubation period, the PHc or PI was incubated for 1 or 2 h with Krebs-Ringer bicarbonate buffer or either of two different concentrations of AZT (1 and 10 µM). In the control incubations, the PHc released less prolactin (PRL) and more follicle-stimulating hormone (FSH) and luteinizing hormone (LH) than the PI, indicating that hypothalamic control of the pituitary was exerted in vitro, presumably by diffusion of releasing and inhibiting hormones from the neurohypophysis to the anterior lobe of the hypophysis. Both concentrations of AZT evoked a significant increase in release of PRL and a decreased release of LH and FSH from the PHc. In the case of LH, the higher concentration of AZT partially suppressed LH release within 1 h. The other effects were not dose-related and were observed after incubating the tissue with AZT for 2 h. However, incubation of the PI with AZT failed to alter anterior pituitary hormone release, illustrating that the site of action of AZT is in the hypothalamus. We hypothesize that AZT blocks DNA synthesis resulting in suppression of synthesis and consequent release of hypothalamic hormones that control release of pituitary hormones in vitro. The results raise the possibility that AZT may alter hypothalamic-pituitary function in vi

ISSN:1021-7401    

DOI:10.1159/000097331

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses.

ISSN:1021-7401    

DOI:10.1159/000097332

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Maternal stress can affect the growth, behavior and immune function of the offspring. Some of these effects are thought to be mediated by maternal glucocorticoids secreted in response to stress. The purpose of the present study was to establish whether dehydroepiandrosterone (DHEA), a weak androgen that is also secreted in response to stress, contributes to the sequelae of prenatal stress in the offspring. Therefore, pregnant rats were treated with different doses of DHEA in the drinking water from day 8 of gestation until parturition, when DHEA treatment was discontinued. Body weights of prepubertal male and female offspring of DHEA-treated dams were significantly and dose responsively lower than those of controls. In contrast, thymic weights were significantly higher in the DHEA offspring. Prenatal DHEA treatment reduced the splenic lymphocyte proliferative response to the T cell mitogen concanavalin A in prepubertal males only, while decreasing the mRNA levels of interleukin-2 receptor alpha and gamma summits. The anterior pituitary expression of pro-opiomelanocortin (POMC) mRNA was increased in prepubertal males only. These data suggest that decreased body weight seen after prenatal stress can be mediated by either DHEA or glucocorticoids. The persistent increase in thymus weight is a new finding that may be very specific to prenatal DHEA treatment. In conclusion, the decreased T cell function and increased POMC expression found in this study indicate that prenatal-stress-induced immune suppression and altered hypothalamic-pituitary-adrenal activity can be, at least in part, DHEA mediated.

ISSN:1021-7401    

DOI:10.1159/000097333

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Thymosin fraction 5 (TF5) is a partially purified preparation of the bovine thymus possessing immunopotentiating properties. TF5 also stimulates the hypothalamic-pituitary-adrenal axis in vivo and anterior pituitary hormone release in vitro. Interleukin-6 (IL-6) is an inflammatory, pyrogenic cytokine that also stimulates hypothalamic and anterior pituitary hormone release. We hypothesized that TF5 may activate the neuroendocrine system in part via the stimulation of central cytokine production. Therefore, we determined the effects of TF5 on IL-6 release from rat C6 glioma cells in vitro. Glioma cells (25–100 × 103) were exposed to vehicle (RPMI-1640) or TF5 (10–1,000 µg/ml) in 96-weIl plates (200 µl incubation volume) for 4–24 h to determine optimal cell number and incubation period conditions. TF5 (1,000 µg/ml) stimulated IL6 release from 100 × 103 C6 cells/well by 9-fold following a 24-hour incubation (p &lt; 0.01). Reducing the number of cultured C6 cells to either 50 or 25 × 103 cells/well resulted in diminished IL-6 responses to TF5. TF5 stimulated C6 cell IL-6 release in a time-dependent manner (4–24 h) at all concentrations tested. A 24-hour incubation period provided the largest TF5-stimulated increases in IL-6 release compared with shorter time intervals (i.e., 4–8 h). Pretreatment of C6 glioma cells with 1 µM phorbol myristate acetate (PMA) for 24 h completely blocked the subsequent stimulation of IL-6 release by PMA (20–250 nM) and partially blocked by 50% the TF5 stimulation of this cytokine. Peptides previously purified from TF5 had no effect on IL-6 release at 50–1,000 nM [i.e., thymosin α1 (Tα1), thymosin β4 (Tβ4), MB35, MB40]. Therefore, TF5 was further fractionated into 7 pools by preparative reverse phase high performance liquid chromatography (HPLC). HPLC pools P1 (fractions 1–8) and P2 (fractions 9–12) significantly increased C6 cell IL-6release (p < 0.01) to the same extent as 250 µg/ml TF5. Other HPLC pooled fractions (P3–P7) had no effect on IL-6 release from C6 glioma cells. P1 and P2 stimulated a 50- and 10-fold increase in IL-6 release, respectively, at a protein concentration of 1.0 µg/ml. Therefore, P1 was more potent and displayed a greater efficacy for the stimulation of IL-6 release compared to P2. Analysis of individual fractions of P1 and P2 revealed that 1 µg/ml of fraction 6 was as efficacious as 250 µg/ml TF5 for the stimulation of IL-6 release. These data indicate that one or more peptide components of TF5 enhance glial cell production of IL-6. In addition, the thymosin-stimulated production of extracellular IL-6 is mediated partially by one or more isoforms of protein kinase C. We hypothesize that a peptide product of the thymus transported across the CNS blood-brain barrier may stimulate the glial cell production of IL-6 and affect neuronal, neuroendoc

ISSN:1021-7401    

DOI:10.1159/000097334

出版商:S. Karger AG    

年代:1997

数据来源: Karger