Psychoneuroimmunology: interactions between the nervous system and the immune system

The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic hypophysiotropic hormones, GH-releasing hormone (GHRH) and somatostatin (SS), exerting stimulatory and inhibitory influences, respectively, on the somatotrope. The two hypothalamic neurohormones are subject to modulation by a host of neurotransmitters, especially the noradrenergic and cholinergic ones and other hypothalamic neuropeptides, and are the final mediators of metabolic, endocrine, neural, and immune influences for the secretion of GH. Since the identification of the GHRH peptide, recombinant DNA procedures have been used to characterize the corresponding cDNA and to clone GHRH receptor isoforms in rodent and human pituitaries. Parallel to research into the effects of SS and its analogs on endocrine and exocrine secretions, investigations into their mechanism of action have led to the discovery of five separate SS receptor genes encoding a f...

Neuroendocrine Control of Growth Hormone Secretion

Cytokines and sleep

The cytokine interleukin-1 (IL-1) has a number of biologic activities, including pronounced effects on the nervous and neuroendocrine systems. In this study, in situ histochemical techniques were used to investigate the distribution of cells expressing type I IL-1 receptor mRNA in the CNS, pituitary, and adrenal gland of the mouse. Hybridization of 35S-labeled antisense cRNA probes derived from a murine T-cell IL-1 receptor cDNA revealed a distinct regional distribution of the type I IL-1 receptor, both in brain and in the pituitary gland. In the brain, an intense signal was observed over the granule cell layer of the dentate gyrus, over the entire midline raphe system, over the choroid plexus, and over endothelial cells of postcapillary venules throughout the neuraxis. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region of the hippocampus, over the anterodorsal thalamic nucleus, over Purkinje cells of the cerebellar cortex, and in scattered clusters over the external-most layer of the median eminence. In the pituitary gland, a dense and homogeneously distributed signal was observed over the entire anterior lobe. No autoradiographic signal above background was observed over the posterior and intermediate lobes of the pituitary, or over the adrenal gland. This study therefore provides evidence for discrete receptor substrates subserving the central effects of IL-1, thus supporting the notion that IL-1 acts as a neurotransmitter/neuromodulator in brain. It also supports studies suggesting that IL-1-mediated activation of the hypothalamic-pituitary- adrenal axis occurs primarily at the level of the brain and/or pituitary gland.

https://www.jneurosci.org/content/jneuro/12/3/1101.full.pdf

In situ histochemical localization of type I interleukin-1 receptor messenger RNA in the central nervous system, pituitary, and adrenal gland of the mouse

The observations and research described in this communication derive from a nontraditional view of the immune system. It has become abundantly clear that there are probably no organ systems or homeostatic defense mechanisms that are not, in vivo, subject to the influence of interactions between behavioral and physiological events. The complex mechanisms underlying these interactions and their relationship to health and illness, however, are imperfectly understood. The most imperfectly understood, perhaps, are the interrelationships among brain, behavior, and immune processes. Without attempting to cover all the literature, we have used stress effects and conditioning phenomena as illustrations to point out that behavior can influence immune function. We have also described data indicating that the immune system can receive and respond to neural and endocrine signals. Conversely, behavioral, neural, and endocrine responses seem to be influenced by an activated immune system. Thus, a traditional view of immune function that is confined to cellular interactions occurring within lymphoid tissues is insufficient to account for changes in immunity observed in subhuman animals and man under real world conditions. These data question seriously the notion of an autonomous immune system. Most of the research on the regulation of immune responses has been predicated on the assumption that such regulation is accomplished by the interacting components of the immune system itself, e.g. interactions among helper and suppressor T-lymphocytes, B-cells, and accessory cells that can result in the production of antibody and effector T cells. The immune system is, indeed, capable of considerable self-regulation, and immune responses can be made to take place in vitro. The functions of that component of adaptive processes known as the immune system that are of ultimate concern, however, are those that take place in vivo. There are now compelling reasons to believe that in vivo immunoregularity processes influence and are influenced by the neuroendocrine environment in which such processes actually take place--an environment that, on the one hand, can generate signals that resting and/or activated leukocytes can receive, and, on the other hand, is exquisitely sensitive to the individual's perception of and capacity to adapt to the demands of the environment. The immune system appears to be modulated, not only by feedback mechanisms mediated through neural and endocrine processes, but by feedforward mechanisms as well. The immunologic effects of learning, an essential feedforward mechanism, suggest that, like direct neural and endocrine processes, behavior can, under appropriate circumstances, serve an immunoregulatory function in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Interactions between the brain and the immune system

In order to determine the possible effects of interleukin-1 on the release of pituitary hormones by direct action on the brain, the peptide was injected into the third brain ventricle of conscious, unrestrained male rats and the effects on hormone release were compared with effects on rectal temperature. The procedure of blood sampling and intraventricular injection resulted in a significant decline in body temperature and a decrease in plasma growth hormone without alteration in the plasma level of thyroid stimulating hormone (TSH) and prolactin. Interleukin-1 injected intraventricularly at a dose of 5 ng (0.3 pmol) prevented the decline in body temperature that occurred in the saline-injected controls and resulted in a significant elevation of plasma growth hormone levels that became apparent within 15 min of injection, as well as a highly variable but significant elevation of plasma prolactin and a significant decline in plasma TSH that was observed at 30 min. The results were similar when areas under the release curves for the various hormones were calculated. On the other hand, the higher dose of 25 ng (1.5 pmole) of interleukin-1, although producing a frank pyrexia, was associated with smaller changes in hormone values, which were no longer significant for any of the three hormones. The results indicate that interleukin-1 can act in minute doses, presumably on structures near the third ventricle, to stimulate growth hormone and prolactin release and to inhibit TSH release. Apparently when frank febrile responses occur, these hormonal responses are muted for reasons that are yet to be determined. In view of the minute doses injected we favor a hypothalamic site for these effects.

V. Rettori

Papers

Central action of interleukin-1 in altering the release of TSH, growth hormone, and prolactin in the male rat.