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At least 775 records · Page 43Linked to original sources
PubMed1999

Hypothalamic beta-endorphin concentrations are decreased in animals models of autoimmune disease.

Complex interactions between the neuroendocrine and the immune systems are present in autoimmune diseases. The central opioid peptide beta-endorphin (BE) has been shown to modulate peripheral immune responses in normal animals. In the present study we analyze the hypothalamic concentrations of this peptide in two models of spontaneous autoimmune disease, the MRL [corrected] lpr/lpr mouse, that develops a lupus-like autoimmune disease, and the obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. In both instances, hypothalamic concentrations of BE are significantly lower than normal controls. In MRL [corrected] lpr/lpr mice, BE is already lower at 1 month of age, when no clinical sign of the disease is yet present. Similarly, low levels of BE are observed in OS chickens before the onset of thyroiditis, i.e., already at the embryonic stage. Moreover, a further decrease of BE is observed in OS chickens in correspondence with the first signs of thyroid mononuclear infiltration. Considering the immunosuppressive effects exerted by central BE, these results are suggestive of the fact that in autoimmune disease prone animals the low hypothalamic concentrations may be one of several factors predisposing for the development of autoimmune disease.

Animals↗
PubMed1999

The role of protective CD8+ T cells in resistance of BALB/c mice to Theiler's murine encephalomyelitis virus-induced demyelinating disease: regulatory vs. lytic.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is an excellent model for human multiple sclerosis. Within the BALB/c strain, BALB/cAnNCr mice are susceptible while BALB/cByJ mice are resistant. BALB/cByJ mice become susceptible when irradiated. Adoptive transfer of CD8+ splenic T cells from resistant BALB/cByJ donors protect irradiated BALB/cByJ, as well as BALB/cAnNCr recipients, from development of TMEV-IDD. Anti-TMEV CTL activities in BALB/cAnNCr, BALB/cByJ and irradiated BALB/cByJ mice are comparable. A population of splenic CD4+ T cells in BALB/cByJ donors has also been identified which can protect both susceptible BALB/cAnNCr and irradiated BALB/cByJ recipients from TMEV-IDD via adoptive transfer.

Animals↗
PubMed1999

Fetal alcohol exposure attenuates interleukin-1beta-induced fever: neuroimmune mechanisms.

Central mechanisms for the attenuating effects of fetal alcohol exposure (FAE) on interleukin-1beta (IL-1beta)-induced fever were studied in adult male offspring of dams fed a liquid diet supplemented with ethanol (E), in pair-fed (P) control and in normal (N) offspring. Hypothalamic levels of IL-1 were significantly lower in E than in N rats at 2 h, but not at 4 and 6 h, after intraperitoneal administration of lipopolysaccharide. Fever induced by intracerebroventricular (i.c.v.) IL-1 was significantly lower in E than in N and P rats. In contrast, E rats showed a normal febrile response to i.c.v. prostaglandin-E2. Thus, whereas FAE does not affect central thermoregulatory mechanisms, per se, FAE alters the kinetics of hypothalamic IL-1 production/appearance and decreases the responsiveness of central mechanisms which mediate the febrile response to IL-1.

Adrenocorticotropic Hormone↗
PubMed1999

Sympathectomy abrogates immunodeficiency associated with protein-energy malnutrition.

The role of the sympathetic nervous system in the immune deficiency developed in protein-energy malnutrition (PEM) was investigated by assessing the effects of sympathectomy on the intestinal immune response of rats subject to prenatal or postnatal malnutrition. Chemical sympathectomy increased the number of IgA+ cells migrating into the intestinal lamina propria of control animals, but this effect was abrogated in rats malnourished during their perinatal stage. The method by which perinatal malnutrition was achieved influenced the magnitude of the effect on serum IgA levels with malnutrition during lactation having a more pronounced depressive effect on IgA than malnutrition during gestation. In experiments in which animals were intestinally immunised with ovalbumin (OVA) the mucosal immune response was reduced in non-sympathectomised malnourished (MN) animals and a lower level of anti-OVA IgA was detected in serum. However, in sympathectomised animals, there was no difference between MN animals and controls in the intestinal and humoral immune responses. The preliminary evidence presented in this paper strongly supports a role for the noradrenergic neurotransmitter system in the immunodeficiency developed during PEM.

Animals↗
PubMed2000

Functional and molecular characterization of VIP receptor--effector system in rat developing immunocompetent cells: G protein involvement.

Changes in the functional characteristics for vasoactive intestinal peptide (VIP) receptor-effector system were evaluated in rat developing immunocompetent cells (from 1-week-old animals up to 12-week-old animals). These characteristics include [125I]VIP binding studies, cell cyclic AMP (cAMP) generation, analysis of [125I]VIP-receptor complexes by cross-linking experiments, as well as developed-associated G proteins assayed by cholera and pertussis toxin-catalyzed ADP-ribosylation and Western blot. The Scatchard analysis of binding data was consistent with the existence of two classes of VIP binding sites with K(d) values unaltered and B(max) increased during postnatal development. The efficiency of VIP stimulation of cAMP generation increased from 1-week-old rats to adult conditions. The VIP-receptor complex apparent molecular mass (52-55 kDa) remains unaltered, but it was significantly lower in 2-week-old than in 8-week-old rats. ADP-ribosylated material by cholera toxin (CTx) was higher from 8-week-old than from 2-week-old animals, while ADP-ribosylation by pertussis toxin (PTx) was quantitatively higher in 8-week-old rats. Results were confirmed when immunoblots for different G protein subunits were performed.

Adenosine Diphosphate Ribose↗
PubMed2000

Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-alpha production by alpha2- and beta-adrenoceptors in mice.

In the present study, the regulation of tumor necrosis factor-alpha (TNF-alpha) production by alpha2- and beta-adrenoceptors located on noradrenergic nerve terminals and on macrophages was studied in endotoxaemic mice. We found that reduction of the sympathetic outflow by reserpine dramatically increased the lipopolysaccharide (LPS)-induced TNF-alpha production, demonstrating that the release of endogenous noradrenaline (NA), controlled by presynaptic alpha2-adrenoceptors, was a determinant factor in this model. By using alpha2- and beta-adrenergic drugs (clonidine, CH-38083, isoproterenol, propranolol) we provided the first in vivo evidence that, beside the dominance of neuronal alpha2- and macrophage beta-adrenoceptors, the alpha2-adrenoceptors on macrophages were also involved in the modulation of LPS-induced TNF-alpha production. Since adrenergic drugs are widely used in the clinical practice, our findings may have therapeutical implications.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics.

Recruitment of inflammatory leukocytes to the injured spinal cord is a physiological response that is associated with the production of cytokines and proteinases that are involved in host defense and wound repair. Cells in the spinal cord are mainly post-mitotic and tissue regeneration is poor; thus, these inflammatory mediators can exacerbate the damage to spared tissue and thereby impair spontaneous functional recovery. Although several aspects of immune function might benefit the CNS, experimental studies indicate that acute neuroinflammation aggravates tissue injury. Until the timing and nature of the molecular signals that govern leukocyte recruitment and activation after spinal injury are defined, clinical therapies designed to boost immune cell function should be avoided.

Animals↗
PubMed2000

Crosstalk between nervous and immune systems through the animal kingdom: focus on opioids.

During the course of evolution invertebrates and vertebrates have maintained common signaling molecules, such as neuropeptides. For example, complete hormonal-enzymatic systems for the biosynthesis of opioid peptides have been found in both the CNS and immune systems of these animals. These signaling molecules have been found in the blood circulation and act as immunomodulators. In vertebrates, release of the signaling molecules occurs during stress (cognitive or pathogens), which triggers the hypothalamo-hypophysial-adrenal axis. Similarly, these neuropeptides are used as messengers to initiate and stimulate the innate immune response in invertebrates. Thus, the crosstalk between nervous and immune systems has an ancient evolutionary origin and the messengers used have been conserved during the course of evolution reflecting their vital importance.

Animals↗
PubMed2003

Acute and conditioned sickness reduces morphine analgesia.

Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. Rev. 23 (1999) 1059]. Thus, we examined whether LiCl, LPS or cues paired with LiCl could reduce morphine analgesia. Morphine analgesia in the tail flick test was reduced 24 h but not 7 days following injection with LiCl, and 24 h following injection with LPS. In addition, morphine analgesia was reduced in the hot plate test 40 min and 24 h following LiCl. Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.

Acute Disease↗
PubMed2000

Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease.

In this review, James Downing and Jaleel Miyan outline emerging evidence for neural mechanisms that contribute to specific categories of host defence. Involvement of direct innervation in the adaptive control of immunological responses complements an established view of neuroendocrine-immune modulation. The challenge remains to understand the integrative and homeostatic functions of 'hardwiring' of peripheral immune effector sites, its bearing on disorder and potential for therapeutic modification.

Afferent Pathways↗
PubMed2000

The brain and thymus have much in common: a functional analysis of their microenvironments.

Research into the neural and immune systems has begun to converge. Since the first reports that interleukins play important roles in both systems and that lymphocytes secrete neuronal factors, scientists have been surprised by the ever-increasing list of interactions. Here, Rolf Mentlein and Marion Kendall examine the major supporting cells of the brain and thymus - astrocytes and thymic epithelial cells - the similar neuroectodermal origin of which could explain such fundamental analogies.

Animals↗
PubMed2001

Elements of angiotensin system are involved in leeches and mollusks immune response modulation.

We present immunocytochemical, biochemical and cellular evidences for the presence of a renin-angiotensin system (RAS) in coelomocytes of invertebrates (leech, Theromyzon tessulatum and mollusk Mytilus edulis). Leech coelomocytes are immunoreactive to polyclonal antisera raised against the T. tessulatum angiotensin-converting enzyme (ACE) and leech brain angiotensin II (AII) and a commercial anti-AT1 receptor. Biochemically, renin, ACE- and AT1-like receptor were identified in the leech immune cells. We further demonstrate that leech AII (10(-6) M) alone does not initiate nitric oxide (NO) release in invertebrate immunocytes but does only after pre-exposing the cells to IL-1 (15.9+/-2.6 nM; P<0.005 vs. 1.1 nM when AII is added alone). Similar results were obtained with human leukocytes (14.5+/-2.7 nM; P<0.005 IL-1+AII vs. 0.9 nM when AII is added alone). Then, an immunocytochemical study performed at the structural and ultrastructural levels confirmed the presence in same immune cells all the molecules of the renin-angiotensin system (RAS) in leeches as epitopes to IL-1-like protein and IL-1-like receptor. This is the first report in invertebrates and of a co-action between cytokines like substances and neuropeptides in an immune process and the involvement of the RAS in modulation of the immune response.

Angiotensins↗
PubMed2003

GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function.

We have recently shown that UDP-glucose, and some related UDP-sugars, are potent agonists of the novel G protein-coupled receptor GPR105 (recently re-named P2Y(14)). GPR105 is widely expressed throughout many brain regions and peripheral tissues of human and rodents, and couples to a pertussis toxin-sensitive G protein. To further characterise the role of GPR105, we demonstrate by immunohistochemistry with receptor-specific antiserum that GPR105 protein is widely distributed throughout the post mortem human brain where it is localised to glial cells, and specifically co-localises with astrocytes. Using quantitative RT-PCR we also show that GPR105 mRNA exhibits a restricted expression profile in an array of human cell lines and primary cells, with prominent expression detected in immune cells including neutrophils, lymphocytes, and megakaryocytic cells. To investigate the G protein selectivity of GPR105, we used chimeric Galpha subunits (Galpha(qi5), Galpha(qo5), and Galpha(qs5)) and an intracellular Ca(2+) mobilisation assay to demonstrate that GPR105 couples to Galpha subunits of the G(i/o) family but not to G(s) family proteins or to endogenous G(q/11) proteins in HEK-293 cells. Finally, we show that expression of GPR105 mRNA in the rat brain is up-regulated by immunologic challenge with lipopolysaccharide. Based on these observations, we propose that G(i/o)-coupled GPR105 might play an important role in peripheral and neuroimmune function in response to extracellular UDP-sugars.

Animals↗
PubMed1999

Cultures of astrocytes and microglia express interleukin 18.

Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell-mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-18. The present results demonstrate that microglia and astrocytes are sources of brain IL-18 and add a new member to the family of cytokines produced in the brain.

Animals↗