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Results for “Neuroimmunomodulation”

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PubMed2004

["Sickness behavior"--mechanisms of origin and significance].

Psychoneuroimmunology, a combination of immunology and neurobiology, is a new field that has emerged over the past 20 years. There is now overwhelming evidence suggesting that the central nervous system is capable of regulating the immune response via two pathways--the autonomic and the neuroendocrine. It is also well documented that the immune system can influence the central nervous system by regulatory molecules or cytokines produced by activated immune cells. In this way, there is a bi-directional communication pathway between the two systems. Sickness behavior seems to present excellent evidence for the existence of immune-system-brain communication. Nonspecific symptoms of infection and inflammation include not only profound physiological but also behavioral changes. Behavioral changes can include anorexia, adipsia, increased sleepiness and depression in social, sexual exploration and general activity. These behavioral changes triggered by pro-inflammatory cytokines are thought to have evolved to conserve the energy necessary to fight infection. They may also minimize infection of conspecifics and reduce susceptibility to predation. Taken together, sickness behavior represents a behavioral reorganization highly motivated to promote survival and recovery. Knowing the mechanisms of neuroimmunomodulation allow us to better understand both the behavioral changes associated with immunotherapy and the changes in immune activation in major depression and other mental disorders.

Animals↗

PubMed1990

[The central nature of the interaction of neuromediator systems in immunomodulation].

The stimulation of immune response is not manifested under blockade of the C2 serotonin receptor by cyproheptadine in animals with lesioned nuclei A9 or caudatus. The control level of the immune response under simultaneous inhibition of the activity of both dopaminergic and serotoninergic systems suggests a central character of their interaction in neuroimmunomodulation.

Animals↗

PubMed1990

[The role of the hypophysis in the immunomodulating influence of the GABA-ergic system].

In CBA mice immunized with the sheep red blood cells (5 x 10(8)), the section of the pituitary stalk prevented the changes in the immune response caused with drugs affecting the activity of GABA-ergic system. Activating effect of the benzodiazepine receptor agonist diazepam, and inhibitory effect of bicucullin on the immune response were not manifest in animals after the lesion of the hypothalamo-pituitary stalk. The mechanism of increasing of the L3T4 T-helpers in bone marrow under the effect of GABA-ergic system activity was also actualized through the hypophysis. The central GABA-ergic mechanisms of the neuroimmunomodulation are discussed.

Animals↗

PubMed1989

[Current physiologic data on sleep].

Sleep is organized as a succession of different physiological states. Despite the fact that the mechanisms which regulate these states has been located in the central nervous system, our knowledge of these regulations is very poor. In this paper, different hypothesis implying brain locations, neurotransmitters, and neuroimmunomodulators are shortly described.

Age Factors↗

PubMedDate not supplied

[Cerebral lateralization and immune response].

Clinical and experimental observations show that the central nervous system can modulate the immune system. Surprisingly, brain immunomodulation may be lateralized as evidenced by two different experimental approaches. The first one consists in unilateral ablation of the brain cortex in rodents. Several lymphocyte and macrophage functions are depressed after lesion of the left cortex whereas the same functions are unchanged or enhanced after symmetrical right ablation. This animal model, useful to elucidate the mechanisms whereby the brain and the immune system can communicate, appears to be suitable for studying the immune perturbations observed during stroke. The second approach is a behavioral one. In humans, an association between left handedness and immune disorders has been described. Likewise, in animals, a lateralized behavior appears to be related to lymphocyte reactivity. Brain asymmetry in neuroimmunomodulation will have an important bearing on theoretical and clinical considerations.

Animals↗

PubMed1993

[The immune response evokes changes of substance P content in some brain areas].

The neuroimmunomodulation (NIM) function of substance P (SP) in some brain areas of rats was investigated by the hemolytic plaque-forming cell (PFC) technique for detecting humoral immune function, and by radioimmunoassay for assessing SP content in some brain areas. The results showed that the contents of SP in the hypothalamus, hippocampus and pons were significantly decreased, while SP contents in the hypophysis, midbrain and medulla were not significantly changed at the peak of the immune response to sheep red blood cells (SRBC). Intracerebroventricular injection of capsaicin and SP antiserum had no effect on the immune response to SRBC. These results suggest that the immune response could affect the metabolism of SP in some brain areas, and provide further evidence that the nervous system (NS) can both regulate immune function and be affected by it.

Animals↗

PubMed1993

[Stress and panic. Immunologic aspects].

Stress induces an imbalance of neuroimmunomodulation, a phenomenon involving the immune, central nervous and endocrine systems. Receptors to substances involved in stress reactions and anxiety, like adrenaline, acetylcholine, histamine, endomorphines, ACTH and several neuropeptides, are present on lymphocytes and lymphocytes can secrete various hormones and neuropeptides. Peripheral and central, cortical and subcortical nervous structures influence immune response. Steroids play a dose dependent inhibitory role perhaps via GIF (Glucocorticoid Increasing Factor) and cytokines (IL 1). In rats, stress induces an increase of corticosterone levels and a lymphopenia depending on the presence of adrenals and pituitary, whereas functional responses to mitogens appear decreased in animals even after surgical removal of adrenals and/or pituitary. Immune response vary according to the degree of control over stressors, to the type of stressor and the animal species. Chronic or repeated stress tends to stimulate immune reaction, contrary to acute stress. In man grief reactions, terminal illness of a spouse, divorce, examinations, caregiving to Alzheimer patients have been used as models of stress, with immune consequences. Pathological anxiety has been less studied, with only few anomalies reported in DSM III-R panic disorder. The immune system participation in the adaptive response to stress is reviewed.

Animals↗

PubMed1997

[Interaction of the epiphysis and the immune system].

First indications that the pineal gland may be involved in endocrine immunomodulation came from early reports on anti-tumor effects of pineal extracts in animals and humans. In the meantime, evidence has accumulated suggesting that melatonin, the major endocrine product of the pineal gland-as a well preserved molecule during evolution-is indeed involved in the feedback between neuroendocrine and immune functions. At present we are beginning to understand the mechanisms of action by which melatonin affects cellular functions, and from the variety of possible direct and indirect interactions it appears that melatonin may play a complex physiological role in neuroimmunomodulation. In this article we present a critical review of the numerous reports on the influence of melatonin on immune functions and discuss the possible underlying molecular pathways. In addition, a short comment is given on the current public discussion as to the clinical value of melatonin.

Animals↗

PubMed1990

Innervation of the guinea pig spleen studied by electron microscopy.

The innervation of the guinea pig spleen was investigated by electron microscopy. Unmyelinated nerve fibers in the capsulotrabecular and arterial systems were found to contain large and small granular and small agranular synaptic vesicles in their terminals and are thought to be sympathetic adrenergic in nature. They influence the contraction of the smooth muscle cells by diffusion innervation in these systems. These nerve terminals were also scattered in both the red and the white pulp. Pulp nerves wrapped by Schwann cells were further enclosed by myofibroblastic reticular cells. This condition revealed that the pulp nerves pass through the connective-tissue spaces of the reticular fibers, which contain elastic fibers, collagenous fibrils, and lamina densa-like materials of the usual basement laminae. One of the target cells for the pulp nerves is considered to be the myofibroblastic reticular cell in the reticular meshwork. Neurotransmitter substances released from the naked adrenergic nerve terminals travel through the reticular fibers and may play a role, by both close association innervation and diffusion innervation, in the contraction of reticular cells to expose the reticular fibers. At the exposed sides, connective-tissue elements of the reticular fibers are bathed with blood plasma, and the included naked nerve terminals, devoid of Schwann cells but with basement laminae of these cells, face free cells at some distance or are in close association with free cells, especially lymphocytes, macrophages, and plasma cells. The close ultrastructural relationship between the naked adrenergic nerve terminals and immunocytes strongly suggests that there is an intimate relationship between the immune system and the sympathetic nervous system through both close association innervation and diffusion innervation. Thus splenic adrenergic nerves of the guinea pig may play a triple role in 1) contraction of smooth muscle cells to regulate blood flow in the organ, 2) induction of the exposure of reticular fibers by contraction of the reticular cells in order to form a close relationship of the nerve terminals with the immunocytes, and 3) subsequent neuroimmunomodulation of the immunocytes.

Adrenergic Fibers↗

PubMed2000

Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes.

Macrophages in lymphoid organs are in close contact to nerve terminals of the sympathetic nervous system. Hence, these cells could be targets of neuronal modulation. We studied sympathetic neurotransmitters as chemoattractants enabling the aggregation of macrophages and nerve terminals. Norepinephrine (NE), neuropeptide Y (NPY), isoproterenol (beta-adrenergic), p-aminoclonidine (alpha2-adrenergic), methoxamine (alpha1-adrenergic), and adenosine triphosphate (ATP) were used to study human monocyte and macrophage migration in 48-well Boyden chambers. NE stimulated chemotaxis of monocytes and macrophages at an optimal concentration of 10-(10) M (P < 0.025). Isoproterenol, but not p-aminoclonidine or methoxamine, induced chemotaxis of monocytes (10(-10) M, P < 0.05). In these studies, elevation of cAMP is a critical step in NE-induced chemotaxis of monocytes. NPY (10(-11) M, P < 0.05) stimulated monocyte chemotaxis as well. ATP at 10(-4) and 10(-5) M stimulated undirected cell mobility (P < 0.05). All tested neurotransmitters of the sympathetic nerve terminal were potent chemoattractants. These findings may explain the close association of nerves and macrophages in tissue and lymphoid organs and may thus be of functional relevance in neuroimmunomodulation.

Chemotactic Factors↗

PubMed1987

Receptors for nerve growth factor on rat spleen mononuclear cells.

Considerable evidence is mounting to support the concept of a modulatory role for the brain and neuroendocrine system on the immune response. This neuroimmunomodulation occurs in part through the interaction of specific neurosubstances with receptors on lymphocytes and monocytes. Nerve growth factor (NGF) is a neuronotrophic factor necessary for the development and maintenance of sympathetic and embryonic sensory neurons. This trophic effect is initiated through binding of NGF at specific cell surface receptor sites on NGF-responsive cells. Several recent studies suggest that NGF may interact with cells of the immune system and may play a role in the regulation of some immunologic reactions. In this study we report on the presence of specific receptors for NGF on the surface of mononuclear cells from rat spleens. The NGF-binding sites are of the low-affinity type with Kd's in the 10(-9) M range. These receptors migrate on SDS-PAGE as two molecular species of approximately 190 and 125 kilodaltons. Our findings of receptors for NGF on lymphocytes and accessory cells support other evidence that NGF may influence immunoreactivity in vivo.

Animals↗

PubMed1995

Serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors.

Serotonin is a well-known neurotransmitter and neuroimmunomodulator which has been reported to modulate T cell and NK cell proliferation. In this study we investigated whether serotonin could regulate mitogen-stimulated proliferation of the mature B lymphocyte. Mouse and rat spleen cells were cultured with serotonin in the presence or absence of a combination of Escherichia coli lipopolysaccharide and dextran sulfate, and proliferation was assessed by [3H]thymidine uptake or propidium iodide staining of DNA. Serotonin alone had no effect on spleen cell proliferation, while it increased mitogen-stimulated B cell proliferation in a dose- and time-dependent manner. These effects were reproduced by the selective 5-HT1A receptor agonist 8-OH-DPAT. Serotonin- or 8-OH-DPAT-induced increase in proliferation could be blocked by the 5-HT1A receptor antagonists (+)WAY 100135 and propranolol. Moreover, lipopolysaccharide-activated mouse spleen cells expressed specific binding sites for [3H]8-OH-DPAT. These results show that serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors, thus providing an important link between this neurotransmitter and the immune system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2003

Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system.

The neurohormone melatonin plays a fundamental role in neuroimmunomodulation of several mammalian species, including mice. This effect is supported by the existence of specific melatonin-binding sites in murine immunocompetent organs. Moreover, using melatonin receptor analogues, several effects of the neurohormone on mice physiology through its membrane and nuclear receptors have been described. The expression of these receptors has never been studied, despite indirect evidence showing the presence of melatonin receptor in the murine immune system. At present, the MT1 and MT2 membrane receptors, and nuclear receptors belonging to the RZR/ROR family have been related to the immunomodulator effect of melatonin. Here, we show the presence of membrane and nuclear melatonin-binding sites in mouse thymus and spleen, using the specific melatonin membrane (S 20098) and nuclear (CGP 52608) receptor agonist. To confirm the presence of melatonin receptors, we analyzed the presence of membrane and nuclear receptor mRNA and protein by RT-PCR, Southern blot, and Western blot. Thus, we show that MT1 and RORalpha receptor mRNA and protein are expressed in both thymus and spleen, while MT2 receptor mRNA is only detected in the thymus. This expression of melatonin receptors strongly supports the idea of an immunomodulatory role of melatonin through its receptors.

Animals↗

PubMed1999

Catecholaminergic, cholinergic and peptidergic innervation of gut-associated lymphoid tissue in porcine jejunum and ileum.

With its abundance of neurons and immunocytes, the gut is a potentially important site for the study of the interaction between the nervous and immune systems. Using immunohistochemical techniques, we tested the hypothesis that gut-associated lymphoid tissue in the porcine small intestine might receive catecholaminergic, cholinergic and peptidergic innervation. Antibodies against protein gene product (PGP) 9.5 were employed to detect neuronal membranes; antibodies against tyrosine hydroxylase (TH), type 2 vesicular monoamine transporter (VMAT-2) and choline acetyltransferase (ChAT) were used to detect catecholaminergic and cholinergic neurons; and antibodies to neuromedin U-8 (NMU-8), substance P (SP) and vasoactive intestinal peptide (VIP) were also used. PGP9.5-immunoreactive nerve fibers were observed between jejunal Peyer's patch (PP) follicles and in submucosal ganglia localized at the base of continuous ileal PP. Many ChAT-positive and a few TH-/VMAT-2-immunoreactive neurons or axons adjacent to jejunal and ileal PP were observed. Neurons and fibers from ganglia situated between or at the base of PP follicles manifested robust immunoreactivities to VIP and NMU-8; relatively less SP immunoreactivity was observed at these locations. All neuromedin-U 8-positive neurons observed exhibited immunoreactivity to ChAT as did some VIP-positive neurons. The specific chemical coding of enteric neurons in close apposition to jejunal and ileal PP and the differential localization of neuropeptides within the jejunal and ileal PP are indicative of neuroimmunomodulation at these sites.

Animals↗

PubMed1990

Prevention of immunosuppression in stressed mice by neurotropin(NSP).

It is well known that the immune function can be compromised by stress. To investigate immune function in mice stressed by experimental restraint or unavoidable and opioid dependent stress, we evaluated the changes in total body weight and in organ weights (liver, spleen and thymus) of these animals, as well as the phagocytic activity of macrophages, the cytotoxicity of T cells and inhibitory effects on tumor growth and changes in T cell subset populations. At the same time we evaluated the effects of Neurotropin (NSP), a substance extracted from the inflamed skin of rabbits inoculated with the vaccinia virus and which appears to possess neuroimmunomodulating activity. The experimentally stressed group exhibited a reduction of phagocytic activity of macrophages, cytotoxicity of T cells and inhibitory effects on tumor growth. In addition there were changes in the population of T cell subsets. In those animals pretreated with NSP, the immunosuppression induced by stress was ameliorated. As compared with several agents which influence phagocytosis, neurotropin exhibited effects similar to that of agents that blocked the adrenaline receptor and an opioid antagonist rather than tranquilizer (diazepam) and a cholinergic receptor blocker. The pharmacologic effects of neurotropin support a relationship between the actions of the central nervous system and the immune system.

Animals↗

PubMedDate not supplied

Asymmetrical brain modulation of the immune response.

It is now well known that the central nervous system can regulate the immune system. Interestingly the two sides of the brain have been demonstrated to be differently involved in the modulation of immune responses. In rodents, lesions of right or left neocortex induced opposite effects on various immune parameters including mitogen-induced lymphoproliferation, interleukin-2 production, macrophage activation or natural killer cell activity. Furthermore in humans, left-handedness has been reported to be associated with a high incidence of immune disorders. Likewise in mice, the direction of a lateralized motor behavior, i.e., paw preference in a food reaching task, correlated with an asymmetrical pattern of brain organization, was shown to be associated with lymphocyte reactivity, natural killer cell activity and auto-antibody production. Conversely the immune system could send to the brain information that may be asymmetrically expressed. The experimental models for investigating asymmetrical brain modulation of the immune system may be useful for studying physiological, pathological and genetic aspects of neuroimmunomodulation.

Animals↗

PubMed1985

Neuroimmunomodulatory interactions of norepinephrine and serotonin.

Monoamine neuroleptics alter rodents responses to immunization, suggesting that norepinephrine (NE) and serotonin (5HT) are neuroimmunomodulatory in these animals. Although endocrine factors participate in their mechanism(s) of action, recent studies suggest that NE and 5HT also interact more directly with immunocompetent cells. This review provides an overview of evidence for a direct regulatory link between the nervous and immune systems and further speculates on the process by which NE and 5HT realize in part, their neuroimmunomodulatory potential. Anatomical data show that noradrenergic fibers of the sympathetic nervous system innervate lymphoid organs providing a channel of communication between neurons and lymphocytes. Presumably neural signals transmitted by NE are received by platelets that in turn, transduce them via 5HT into immunomodulatory messages. It is proposed that NE alters the capacity of platelets to sequester and/or catabolize 5HT, thus regulating its physiologically active pool in the plasma. Macrophages possess a 5HT uptake system, the kinetic properties of which make them sensitive to changes in plasma levels of the amine. Thus, through its ability to regulate plasma levels of 5HT, an immunosuppressive amine with access to macrophages, the nervous system can influence cells involved in antigen recognition. Support for this hypothetical immunomodulatory mechanism is gleaned from clinical and experimental studies. For example, individuals suffering emotional trauma are more susceptible than others to developing physical illness. It is of interest that platelet 5HT pharmacodynamics are often abnormal in patients with psychological disorders characterized by catecholamine deficits. Similar platelet changes have been achieved experimentally by treating rats with catecholamine antimetabolites. Additional support for the hypothesis derives from aging research since 'monoamine imbalance' and immune dysfunction are co-characteristics of senescence. In aging rodents and humans, central catecholamine deficits are associated with a decreased platelet affinity for 5HT and an increased plasma content of 5HT. Thus, emotional, spontaneous (age-related), or experimental changes in monoamine homeostasis have the potential to increase the risk of disease in affected individuals. Perhaps part of this effect results from endocrine perturbations associated with the trauma. However, a direct interaction between the nervous and immune systems involving monoamines is also possible, and a need for future study of this potentially significant mechanism for neuroimmunomodulation is indicated.

Aging↗

PubMed1992

Presence of endo-oligopeptidase (EC 3.4.22.19), a putative neuropeptide-metabolizing endopeptidase in cells of the immune system.

Neuropeptides have been shown to modulate the bidirectional communication between the central nervous and immune systems. The endooligopeptidase (EC 3.4.22.19), originally isolated and characterized in the nervous tissue, was shown to hydrolyse several neuropeptides and to generate enkephalin from enkephalin-containing peptides. This report shows the presence of endopeptidase 22.19 in the rat immune system using both biochemical and immunochemical methods. The specific activity of endopeptidase 22.19 in soluble fraction of lymphocytes was 3-4-fold higher than the one found in the nervous tissue. Among rat blood cells the highest specific activity of endopeptidase 22.19 was found in T lymphocytes, being 2.5-fold higher than the activity found in other leukocytes. Immunocytochemical studies performed in tissues and cells of the immune system indicate the presence of endopeptidase 22.19-like enzyme in all types of leukocytes. The occurrence of this enzyme in cells of the immune system can be considered an important step in understanding the metabolism of neuropeptides in the immune system as well as its possible participation as a regulatory enzyme in neuroimmunomodulation.

Animals↗