Archives 1992-2013

2004, volume 13, suplement 1

Brain immunology

Mutual interactions between the immune and neuroendocrine systems

Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 5-11

Aim. To present the contemporary knowledge on interactions between the immune system and neuroendocrine system.

Review. On the cellular and molecular levels, mutual interactions of these homeostatic systems are based on the existence of shared receptors and their ligands: cytokines (including endogenous opioids), hormones, and neurotransmitters. The nature of functioning of both the innate immunity (with participation of phagocytes) and acquired adaptive immunity (with participation of lymphocytes) is outlined. The immune system response to antigenic stimulation is accompanied by activation of the hypothalamic-pituitary-adrenal stress axis, sympathetic nervous system, and of the endogenous opioid system. On the other hand, the immune reactions are modified by physical and psychological stressors, which results – depending on numerous additional factors –either in enhancement or inhibition of their components.

Brain immunology

Neuroimmunology of schizophrenia and depression

Janusz Rybakowski
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 13-21

Aim. To review the most significant data concerning the immunological system importance in the pathogenesis and treatment of schizophrenia and depression.

Review: There are three aspects of the immunological system role in the pathogenesis of schizophrenia: contribution of the autoimmune process, cytokine regulation disturbances, and a pathogenic effect of viral infections. The studies carried out in depressed patients in the 1980s reported a reduction in the immunological system activity (particularly of cellular immunity). On the other hand, research findings obtained in the 1990s indicate a pathological activation of this system, with probably a major role of the cytokine system disturbances, especially of the so-called pro-inflammatory cytokines. Both experimental and clinical studies suggest an antiviral and immunomodulatory action of lithium salts. In the review some data are also presented pertaining to neuroimmunological aspects of the action of neuroleptic and antidepressant drugs, as well as their possible therapeutic effects in schizophrenia and depression via the immunological system.

Brain immunology

Interrelatianships between melatonin and the immune system

Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 23-34

Aim. To summarize the present knowledge on functional connections between the pineal gland and immune system, with a special emphasis on the immunomodulatory effects of melatonin in humans.

Review. The pineal gland is a vertebrate neuroendocrine organ, transforming external photic signals into a biochemical message, comprehensible to all the cells of the organism. The signal is melatonin, synthesized and released into the bloodstream in a rhythmical manna, with a low level during the day and an increase at night. The same circadian rhythm of melatonin exists in all animals, irrespective of their circadian locomotor activity pattern. Melatonin is involved in the regulation of a majority of processes subject to circadian and seasonal rhythms, including body temperature and sleep in humans, breeding of wild-living animals, seasonal changes in their immune system activity, etc. Being a potent free-radical scavenger, it actively protects organisms against oxidative stress. Melatonin acts also on immune cells – directly, via specific receptors, and indirectly, through modification of the level and circadian rhythms of several other hormones involved in immunomodulation. Activated immune cells, in turn, synthesize and release the soluble message molecules, cytokines, influencing the biosynthesis of melatonin. Therefore, the pineal gland and melatonin are involved in the regulatory circuit composed of the nervous, endocrine and immune systems, responsible for the maintenance of homeostasis within the vertebrate organism.

Brain immunology

Cytokines and depression

Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 35-41

Aim. To present the role of immunoactivation associated with pro-inflammatory and neurodegenerative processes in the onset of depression symptoms.

Review. In depressed patients without any concurrent pro-inflammatory disease of known etiology, increased levels of pro-inflammatory cytokines and other markers of inflammatory process are observed. On the other hand, increased susceptibility to depression has been reported in patients with an elevated serum level of pro-inflammatory cytokines resulting from on-going inflammatory processes (e.g. rheumatoid arthritis). Psychological stress leads to an increase in the production of pro-inflammatory cytokines and at the same time may contribute to the development of depressive symptoms. Immunotherapy using pro-inflammatory cytokines of some neoplastic diseases and chronic type C hepatitis results in depressive states. Administration of pro-inflammatory cytokines or lipopolysaccharide (which activates cytokine secretion) to laboratory animals evokes a state resembling depression. In neuroimaging studies the same changes in the activity of cerebral structures have been found in depressed patients and in those receiving cytokine immunotherapy. Antidepressants eliminate depressive states induced by the administration of pro-inflammatory cytokines, and besides, inhibit the synthesis of pro-inflammatory cytokines in vitro. The latter findings confirm the role of cytokines in the onset of depression and suggest that therapeutic action of these drugs may be connected with their immunosuppressive effect.

Brain immunology

The immune-mediated diseases of the nervous system

Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 43-60

Aim. The article presents a review of immune-mediated diseases of the nervous system .Review: For a long time the central nervous system (CNS) has been thought to be immunologically passive. Among potential reasons of the CNS immune passivity the following have been listed: the presence of the blood-brain barrier (BBB), lack of lymphatic drainage, absence of dendritic cells capable of antigen presentation, low expression of antigens of the major histocompatibility complex (MHC), and short lifetime of immune cells entering the CNS. However, many data suggest that the state of the CNS immune passivity is not absolute: a) diffusion of intraparenchymatous fluid from the brain into lymphatic nodules and peripheral blood is possible, b) activated T and B cells are capable of crossing the BBB, c) immune-modulating molecules (antibodies, cytokines) can get into the CNS, d) in response to a variety of stimuli microglial and astroglial cells express MHC class I and II molecules, e) the CNS cells are capable of cytokine secretion.

Conclusions. There is an increasing body of evidence confirming the role of immune response in the pathogenesis and course of many pathological conditions of the nervous system, including polyneuropathies, demyelinating syndromes, neuromuscular disorders, paraneoplastic syndromes.

Brain immunology

The inflammatory reaction in neurodegenerative disorders – detrimental or neuroprotective?

Postępy Psychiatrii i Neurologii, 2004, 13, suplement 1 (17), 61-71

Aim. To present an essential role of inflammatory processes in the pathogenesis of neurodegenerative diseases.

Review. Neurodegenerative processes in the central nervous system (CNS) are typically associated with microglial activation, astrogliosis and increased expression of inflammatory molecules. The presence of activated microglia and T lymphocytes, as well as an elevated expression of complement proteins and a variety of cytokines have been reported in Alzheimer s and Parkinson's diseases, amyotrophic lateral sclerosis and other neurological disorders. However, the role of inflammation in the CNS is still far from clear. Some research findings indicate that prevention of inflammatory reaction development reduces the damage to nervous cells, while other data suggest it has an opposite, destructive effect, resulting either in the nervous tissue accelerated degeneration or in hampering of its regeneration. A particular role in the immunological response regulation is ascribed mainly to T CD4+ lymphocytes considered to be responsible for the observed effect of protective inflammation. Interestingly, T lymphocytes, by means of trophic factors production, can protect neurons and stimulate their regeneration. However; T lymphocytes il1flux in to CNS is limited by mechanisms protecting the organism against autoimmune disease development. The possibility of reducing this limitation by proper vaccination with myelin proteins or by administration of activated T lymphocytes is being intensely studied.