Advances in neuroimmunology最新文献

Recent evidence indicates that the neuroendocrine and immune systems are intimately integrated into one system that provides a complex homeostatic network. Disruption of one system by extrinsic factors such as stress or antigenic exposure usually has consequences on the other. With advancing age, a progressive disruption can be observed in both systems which may have profound implications with respect to age-associated pathologies, including autoimmunity. In this review evidence is summarized which supports the hypothesis that neuroendocrine factors influence the age-associated decline of the immune system.

The aim of this review is to provide a comprehensive examination of the current literature describing the immunoregulatory effects on the peripheral immune system by the hormones that comprise the hypothalamic-pituitary-thyroid (HPT) axis. This article discusses the effects of the HPT axis hormones on the peripheral lymphoid tissues and the immune responses mediated by the cells that comprise these lymphoid tissues. Neuroendocrine dysfunction in the HPT axis, either naturally or experimentally induced, and the resulting immune dysfunction are also discussed. Emphasis in this article is placed on the most recent study findings and those that provide a unique or novel way of evaluating HPT hormone effects on the immune system. Our knowledge of the immunoregulatory effects of the hormones that comprise the HPT axis has grown tremendously in the last 10 years. As can be seen in this review, the immunoregulatory effects of the HPT axis hormones are quite diverse and influence most, if not all, aspects of immune system physiology. The continued exploration of the bidirectional circuitry between the immune and neuroendocrine systems may allow for development of appropriate prophylactic procedures that prevent dysfunction in both systems.

The results discussed here indicate that under the conditions of restraint stress and under the control of CNS, a suppressive protein (NIP) was generated in peripheral lymph tissue and released into the blood stream, which acts as a immune suppressor. It is potentially a very important molecule that could be very important to our understanding of the interaction between CNS and immune function.

The aim of the review is to summarize our recent studies on the influence of the thymus on liver functions and its intermediary pathway in rats. Young adult thymectomized rats were used as a model in the experiments, and either thymic peptides or sex hormones were supplemented to these animals. Liver microsomal cytochrome P-450 and aminopyrine-N-demethylase (ADM) activities were decreased in thymectomized rats, and the change in the male was more significant than that in female rats. An increase of liver malondialdehyde (MDA) and a decrease of liver glutathione (GSH) and superoxide dismutase activity were observed in the female thymectomized rats, but not in the males. Accompanied by the increase of MDA, a decline of membrane fluidity of liver microsomes and mitochondria and a decrease of Ca²⁺ uptake by liver microsomes were exhibited in the female thymectomized rats. Subcutaneous injection of thymic peptides decreased MDA level, and increased GSH content, membrane fluidity and Ca²⁺ uptake by microsomes in the liver of thymectomized rats. On the other hand, male thymectomized rats showed a decrease of hypothalamic luteinizing hormone-releasing hormone (LHRH), plasma luteinizing hormone (LH) and testosterone levels. Subcutaneous injection of testosterone propionate to these animals restored their liver P-450 and ADM activities to normal levels. Female thymectomized rats exhibited a decline of hypothalamic LHRH and plasma estradiol levels. Supplementation of estradiol benzoate reversed the increase of liver MDA in these animals. The data suggest that the thymus may influence liver functions through the hypothalamus-pituitary-gonad axis. Thus, a new ‘thymus-neuroendocrine-liver pathway’ is proposed, which may account for the significance of the thymus in maintaining homeostasis and integrative functions in the body.

The interactions between the immune system and psychological states are both intricate and intriguing. Research at a molecular level has thrown considerable light on the previously ill-defined area of psychoneuroimmunology. In this report, we explore the psychoneuroimmunology of autoimmune disorders, particularly rheumatoid arthritis and lupus erythematosus. Animal models of these diseases have provided a particularly useful window on complex psychoneuroimmunological interactions. Observations about the effect of stress on the onset and course of autoimmune disorders has added to our understanding of psychoneuroimmunological interactions. These interactions are bi-directional, as reflected in the autoimmune-mediated neuropsychiatric manifestations of systemic lupus. Exploring the role of various neurotransmitters and neuromodulators in the stress response may have important therapeutic implications for autoimmune disorders.

Experimental evidence is accumulating showing that vasoactive intestinal peptide (VIP) acts as an immunoregulatory peptide. Findings from our laboratory and others indicate that cells of the immune system are able to produce VIP. We have detected immunoreactivity for VIP in lymphocytes by immunohistochemical methods at specific locations of both central and peripheral lymphoid organs. Double immunofluorescence staining and flow cytometry analysis indicate that both T and B lymphocytes contain VIP that has been proved to be mostly VIP_1–28 by high-performance liquid chromatography and radioimmunoassay. VIP has been also demonstrated by ‘in situ’ hybridization and reverse transcription followed by polymerase chain reaction. We have also detected induction of VIP in splenic lymphocytes after mitogenic stimulation. Lymphocytes should be sensitive to the endogenously produced VIP because we have also detected VIP receptor expression in different populations of lymphocytes. All this evidence indicates that VIP is an endogenous autocrine modulator of immune function.

The nervous and endocrine systems modulate the immune system functions through releasing neurotransmitters, neuropeptides and endocrine hormones as they regulate the other physiological functions. The immune system in turn communicates with the nervous and endocrine systems through secreting immunocompetent substances. In this report we review our concepts and evidence concerning the immunoregulatory role of acetylcholine (ACh) and monoamine neurotransmitters which include noradrenaline (NA), 5-hydroxytryptamine (5-HT) and dopamine (DA). The immunoregulatory role comprises two aspects, the modulation of immune functions by neurotransmitters and the effect of the immune system on nervous system functions. The inhibition of ACh biosynthesis in the central nervous system (CNS) caused the enhancement of the humoral immune response of rats to sheep red blood cells (SRBC); by contrast, the inhibition of acetylcholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role. The role can be blocked by atropine, a muscarinic antagonist, but not by hexamethonium, a nicotinic antagonist. During the humoral immune response (days 3–6 after SRBC injection), activity of AChE in the hypothalamus and hippocampus was strikingly lower. It is suggested that a functional connection is present in the ACh of the brain and the immune system. In vitro, ACh at 10⁻⁹ to 10⁻⁴ mol/l dose range significantly strengthened the spleen cell proliferation induced by concanavalin (Con A). The action of ACh only occurred either before or just after T lymphocytes were activated through muscarinic cholinergic receptors. In vivo, the depletion of monoamine neurotransmitters or only NA in the CNS caused the impairment of the anti-SRBC response of rats. During the phases of days 2–7 post-immunization, the metabolic alterations of NA, 5-HT and DA emerged in the CNS and the lymphoid organs of rats, which mainly exhibited that in the peak periods of the antibody response, the metabolism of the monoamine neurotransmitters in the hypothalamus and hippocampus was markedly increased, but NA content in the spleen and thymus was significantly decreased. These results provide evidence for the bidirectional information exchange network between the monoamine neurotransmitters and the immune system. Exposure to NA (at 10⁻⁸–10⁻⁵ mol/l concentration range) in vitro was shown to inhibit the Con A-induced proliferation of the rat spleen cells. This effect of NA was related to the early events involved in the initiation of T cell proliferation and was mediated by either alpha- or beta- adrenergic receptors. The evidence that altering 5-HT level in the central or peripheral nervous systems through various ways of administering the drugs to regulate 5-HT biosynthesis led to the variations of the antibody response, and that cyproheptadine, a