Neuroendocrine-immune System Research Articles

Do local immune-neuroendocrine disturbances initiate diabetes?

It has been suggested that there exists a local immune-neuroendocrine self-regulating system in the pancreas. The system consists of beta-cells, nerve ganglia, intercellular fluid, connective tissue, and endothelial and immunocompetent cells. The local immune-neuroendocrine system governs the background level of insulin production by intrinsic mechanisms both in normal conditions and in a recovery period after different kinds of stress. The activity of this system by a complex of metabolic, environmental, nerve, and nonspecific immune factors has been determined. The local immune-neuroendocrine system is partially autonomous as a result of local integrative nerve circuits, morphological and functional substrates. Increased or decreased synthesis and release of some cytokines or biologically active substances (neurotransmitters, neuropeptides, gamma-aminobutyric acid, metabolites, nitric oxide, ions, etc.) by various cell types in the local immune-neuroendocrine system above usual levels may result in disturbances of sensitivity and functions of beta-cells. If the capability of the local immune-neuroendocrine system is insufficient for their compensation, the islet cell autoantigens may occur, the specific immune mechanisms are involved, and the pathological process becomes irreversible. Some ways for prevention of disturbances in the local immune-neuroendocrine system during the early and late phases of diabetes are presented.

Study of different patterns of immuno-modulatory mechanism by tonifying Kidney and Invigorating Spleen drugs

Objective: To observe the acting pattern on the immune system by Kidney tonifying (KT) drugs.Methods: Three composite recipes were used on the 7- and 14-day corticosterone rat model to study the effect of recipes on the different patterns of immuno-modulatory and neuro-endocrinological systems.Results: The immune system of Spleen Invigorating (SI) group was well protected in either 7- or 14-day experiments, with the SI recipe showing no effect on the neuroendocrine system. It suggested that SI recipe might have direct action on immune system. On the other hand, KT group with no effect on neuroendocrine-immune (NEI) system in 7-day experiment, but showed a remarkable protective effect of the whole NEI system in 14-day experiment.Conclusion: The results indicated that KT recipe acts on the neuroendocrine system first, and then influence the immune system. It means that the action took place through down pathway of NEI network.

Cellular responses to moderate and heavy exercise

Moderate and heavy exercise induce a multitude of changes in the neuroendocrine immune system, the net effects of which depend on various other factors including the host's physical condition, and the intensity and duration of the exercise bout. Most investigators report that the risk of upper respiratory infection is increased following heavy exertion, but is decreased after moderate exercise. Many heavy exercise-induced changes in the host's immune defenses are consistent with the alterations reported in classical stress studies; some consensus has been achieved in this area that heavy exertion may indeed elicit responses common to psychological forms of stress. The immunomodulation consists, most notably, of shifts in the number and function of circulating innate and adaptive immune cell populations apparently in response to the release of classical stress hormones and cytokines, and expression of selectin and adhesin molecules. Rapid trafficking of cells in and out of the blood compartment in response to exertion probably mirrors the demand for certain cell types in specific tissues, a hypothesis requiring verification in animal models and ultimately the human. Also needed are studies correlating the functional status of the circulating cells with those in the tissues.Key words: neuroendocrine immune system, exercise-induced stress, upper respiratory tract infections, immunomodulation, immune defenses.

Cellular responses to moderate and heavy exercise.

Moderate and heavy exercise induce a multitude of changes in the neuroendocrine immune system, the net effects of which depend on various other factors including the host's physical condition, and the intensity and duration of the exercise bout. Most investigators report that the risk of upper respiratory infection is increased following heavy exertion, but is decreased after moderate exercise. Many heavy exercise-induced changes in the host's immune defenses are consistent with the alterations reported in classical stress studies; some consensus has been achieved in this area that heavy exertion may indeed elicit responses common to psychological forms of stress. The immunomodulation consists, most notably, of shifts in the number and function of circulating innate and adaptive immune cell populations apparently in response to the release of classical stress hormones and cytokines, and expression of selectin and adhesin molecules. Rapid trafficking of cells in and out of the blood compartment in response to exertion probably mirrors the demand for certain cell types in specific tissues, a hypothesis requiring verification in animal models and ultimately the human. Also needed are studies correlating the functional status of the circulating cells with those in the tissues.

Study of different pattern of immuno-modulatory mechanism by tonifying Kidney and invigorating Spleen

To observe the acting pattern on the immune system by tonifying the Kidney (TK). Three composite recipes were used on the 7- and 14-day corticosterone rat model to study the effect of recipes on the different pattern of immuno-modulatory and neuroendocrinological systems. The immune system of Invigorate the Spleen(IS) group was well protected in either 7-day or 14-day experiment, without any effect of IS recipe acting on the neuroendocrine system, it suggested that IS recipe might have direct action on immune system, while TK group with no effect on neuroendocrine-immune (NEI) system in 7-day experiment, but showed the remarkable protective effect of the whole NEI system until 14-day experiment. The results indicated that TK recipe is acting on the neuro endocime system first, and then influence the immune system. It means that the action was through down pathway of NEI network.

Inhibitory effect of pregnancy on stress-induced immunosuppression through corticotropin releasing hormone (CRH) and dopaminergic systems

To clarify the involvement of pregnancy in the response of the neuroendocrine–immune system to stress, we examined splenic natural killer cell activity (NKCA) and its relevant central and blood parameters in female virgin and pregnant rats (10 to 11 days gestation) exposed to forced water-immersion stress with durations of 90 min and 180 min. Decreases in splenic NKCA, corticotropin releasing hormone (CRH) in the hypothalamus, and increases in progesterone (P), β-endorphin ( β EP), and dopamine (DA) metabolic ratios in the frontal cortex and nucleus accumbens produced by stress were recognized in the virgin rats, but not in the pregnant rats. Pregnancy reduced splenic NKCA in rats without stress, but elevated it in the rats exposed to stress with a duration of 180 min. These findings suggest inhibitory effects of pregnancy on stress-induced immunosuppression and neuroendocrine changes, thereby promoting homeostasis in the neuroendocrine–immune system against stress. Such enhanced homeostasis associated with pregnancy seemed to be mediated by the activation of placental P and placental or pituitary β EP in cooperation with mesocortical and mesolimbic DA systems and hypothalamic CRH.

Role of the Cytokines in the Neuroendocrine-Immune System Axis

A rapidly growing body of evidence reveals that complex networks of communication exist between the neuroendocrine and the immune systems. Essential to the maintenance and function of the immune-endocrine circuitry are an array of chemical mediators produced by cells of the immune and endocrine systems. Cytokines are glycoproteins (molecular masses of 15,000-20,000) that are elaborated by antigen-activated immune cells and responsible for orchestrating immune cellular activities. These inflammatory mediators also affect the functioning of the neuroendocrine system. Thus, interleukin-1 (IL-1), IL-2, IL-4, IL-6, tumor necrosis factor-α and interferon-γ affect the secretion of hypothalamic and anterior pituitary hormones in vitro and in vivo, and specific high-affinity receptors for IL-1, IL-2, and IL-6 have been identified in neuroendocrine tissues. A paracrine role for these factors in the regulation of neuroendocrine function may be advanced because certain of these mediators (e.g., IL-1, IL-6) are present in the hypothalamus as well as the anterior and neurointermediate lobes of the pituitary. The production of these cytokines in neuroendocrine cells is enhanced by neuropeptides, endotoxin, and other cytokines. We propose that the local neuroendocrine cytokinergic tone may act in a facilitative manner to enhance the secretion of hypothalamic-pituitary hormones.

Consequences of restraint stress on natural killer cell activity, behavior, and hormone levels in rhesus macaques ( Macaca mulatta)

Three experiments were performed to determine the effect of stress on the neuroendocrine-immune system in nonhuman primates. In Experiment 1 the diurnal variation in cell and hormone levels was determined. The percentages of neutrophils, monocytes, and eosinophils fluctuated throughout the 24-hr period, while white blood cell (WBC), neutrophil-to-lymphocyte ratio (N:L), hemoglobin (Hgb), natural killer cell cytotoxicity (NK activity) and β-endorphin levels did not. Experiment 2 investigated the effects of ketamine and restraint on behavior. Scratching was increased in control monkeys and animals receiving ketamine, whereas passivity was increased in chair-restrained animals. In Experiment 3, eight adult male rhesus monkeys were restrained in primate chairs at 0600h. Behavior was filmed for 3 hr and blood samples were collected at 0700, 0800, and 0900. Whole blood was analyzed for total WBC and percentage of each leukocyte type. NK activity was also measured. Plasma levels of cortisol and β-endorphin were determined and behavior was quantitated from video-records. WBC and the percentage of neutrophils increased during the restraint period, while the percent lymphocytes and monocytes decreased. NK activity also decreased over time after restraint whereas plasma cortisol and β-endorphin levels increased significantly. Although after the 3 hr of restraint stress, changes were found in hormone levels, behavior, and NK activity, there were no significant correlations between the parameters measured. Thus, our results indicate that there is not a common neuroendocrine response or single neuroendocrine mediator that results in predictable behavioral changes and immune suppression following stress.

Phylogeny of the neuroendocrine-immune system: Fish and shellfish as model systems for social interaction stress research in humans

Significant interactions among various physiological systems and between an organism's physiological and psychological structures are evident throughout phylogeny. Environmental stimuli induce neuroendocrine responses that include the activation of the sympathetic nervous system and of the hypothalamic-pituitary-adrenal (HPA) axis, and that modulate cellular and humoral host defense mechanisms from the invertebrates to humans. Because increased levels of HPA products are among the most consistent physiological responses to stress, and bacause cell-mediated immune (CMI) mechanisms are crucial to the initiation, propagation, and regulation of antigen-specific immune responses, this review focuses on the phylogeny of HPA-CMI interaction under basal conditions and following stressful stimuli. Research has characterized several paradigms for the study of the physiological outcomes to a variety of stressors. In recent decades, a substantial literature has emerged that describes the neuro-endocrine-immune response to social confrontation in invertebrates and in vertebrates. The social confrontation paradigm provides an ideal model for the elucidation of the phylogeny of the HPA-CMI interactive system to a specific stressful stimulus. We have characterized the neuroendocrine-immune outcomes of social confrontation in fish. Our data help to explain physiological and pathological mechanisms in fish. Implications of this body of knowledge to clinical medicine and aging are discussed.

Neuroendocrine-immune interactions associated with loss and restoration of immune system function in spinal cord injury and stroke patients.

Both natural and adaptive immune responses were shown to be strikingly decreased in initial blood samples from 34 spinal cord injury and stroke patients. NK-cell function decreased to 24.8% (mean) 2 weeks after spinal cord injury in previously healthy young adults whose control group revealed a mean NK-cell function of 48.7%. This was accompanied at 2 weeks by increased plasma ACTH (mean of 17.0 pg/ml from 17 patients compared to a mean of 11.2 pg/ml from 12 controls) and urine free cortisol levels (mean of 152.1 micrograms/24 h from 9 patients compared to 53.6 micrograms/24 h from 15 controls). T-cell function and/or activation decreased to below normal values within 3 months after injury as revealed by lymphocyte transformation that was 32.8% of normal at 3 months. T-cell activation diminished as shown by a mean IL-2 receptor level of 179.3 units/ml in patients compared to 328.2 units/ml in controls. Serial monitoring of NK- and T-cell function revealed that specific physical rehabilitation therapy over a period of 6 months after injury restored NK- and T-cell function to near normal levels in most patients. This improvement was accompanied by a parallel rise in the patient's functional independence measurement scores. Results suggest critical neuroendocrine-immune system interactions in the restoration of immune function. Cortisol levels reverted to normal after 6 months of rehabilitation. Limited data suggest that natural immune system depression, NK-cell function, persists in spinal cord injury patients not receiving rehabilitation therapy (mean NK-cell lysis of 10.3%; p < 0.01).

ACTH-like molecules in gastropod molluscs: a possible role in ancestral immune response and stress

The presence of immunoreactive ACTH molecules on phagocytic cells from the freshwater snails Planorbarius corneus and Lymnaea stagnalis was shown by cytofluorimetric analysis. The role of ACTH in phagocytosis and in the release of biogenic amines, two biological responses that may be taken as ancestral types of immune response and stress, respectively, has also been evaluated. ACTH markedly increased the phagocytosis of Staphylococcus aureus by P. corneus haemocytes and caused the release of biogenic amines from such cells into the serum. These data, as well as tracing the ancestral physiological role of ACTH, favour the hypothesis that immune and neuroendocrine systems share a common evolutionary origin.

Disturbances in neuroendocrine-immune system in anorexia nervosa (AN)

Disturbances in neuroendocrine-immune system in anorexia nervosa (AN)

Disturbances in neuroendocrine-immune system in anorexia nervosa (AN)

Disturbances in neuroendocrine-immune system in anorexia nervosa (AN)

Unique subset of thymic epithelial cells defined by the expression of a novel neuroendocrine antigen

Murine monoclonal antibodies (MoAbs) were produced against a rat medullary thyroid carcinoma to identify neuroendocrine differentiation antigens. One of these antibodies (1D4) identified a novel 62- to 69-kDa antigen expressed by subsets of immune system epithelial and neuroendocrine cells. This antigen is expressed by distinct subsets of thymic epithelial and splenic reticular cells and is shared by discrete subsets of anterior pituitary and thyroid neuroendocrine cells. In the thymus, 1D4 expression identified a unique subset of stellate-shaped Ia + medullary epithelial cells which did not react with thymosin alpha-1 antisera nor with the MoAb A2B5 specific for a GQ ganglioside expressed by thymic hormone-producing cells. The availability of the 1D4 MoAb should facilitate further characterization of 1D4 + immune system epithelial cells and may advance our understanding of neuroendocrine-immune system interactions.