Brain immune system activation

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

The sympathetic nervous system (SNS) and the hypothalamic-pituitary axis work together as important modulators of the immune system after exposure to stressors. Norepinephrine (NE) and epinephrine (EPI) (catecholamines from the SNS) and neuroendocrine hormones modulate a range of immune cell activities, including cell proliferation, cytokine and antibody production, lytic activity, and migration. This chapter will focus on these two major pathways of brain-immune signaling, briefly summarizing the evidence for SNS and hypothalamic-pituitary-adrenal (HPA) modulation of immune function, their influence on immune-mediated diseases, immune modulation in aging, and early life influences on these pathways. 

Little is known about the molecular mechanisms and complexity converting psychosocial stress into cellular dysfunction in the brain, endocrine, and immune systems. How ordinary and sustained maladapted psychosocial stressors, chronic stress, and an unhealthy lifestyle activate and exert an influence on the biochemistry of the neuro-endocrine-immune axes with implications for future health or disease, is an upcoming innovative research field due to the new and emerging fields of proteomics, metabonomics, and biochip technologies. 

With this background there is an obvious call for novel strategies to follow changes of complex molecular patterns of different stress-related diseases over days, weeks, months, and years as an effect of lifestyle and the psychosocial environment to reflect the effects of unhealthy environments. The molecular interactions between the brain and the immune system in health and disease are reflected in the circulatory system as the white blood cells, the lymphocytes, mimic ongoing activities in the brain. By using lymphocytes from patients with psychosomatic-psychiatric diseases we can find detailed information about protein-peptide translational modifications and transformation essential for the development of new approaches that can prevent and treat major psychiatric diseases. 

They are precursors for the synthesis of glucose via glu-coneogenesis that is required for the increased number and activity of cells of the immune system, for those involved in repair (e.g. fibroblasts) and for the brain, especially if the patient cannot feed. 

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

These smoked substances interact with the brain s own cannabinoid receptors to trigger dopamine release from the mesolimbic reward system. There are two known cannabinoid receptors, CB1 (in the brain, which is coupled via G proteins and modulates adenylate cyclase and ion channels) and CB2 (in the immune system). The CB1 receptors may mediate not only marijuana s reinforcing properties, but also those of alcohol. There is also an endogenous cannabinoid system (the brain s own marijuana) capable of activating these cannabinoid receptors functionally. These ert-docannabinoids are synthesized by neurons and inactivated by reuptake systems and enzymes in both neurons and glia. 

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop that includes the hypothalamus, the pituitary and the adrenal glands. The main hormones that activate the HPA axis are corticotrophin releasing factor (CRF), arginine vasopressin (AVP) and adrenocorticotrophic hormone (ACTH). The loop is completed by the negative feedback of cortisol on the hypothalamus and pituitary. The simultaneous release of cortisol into the circulation has a number of effects, including elevation of blood glucose for increased metabolic demand. Cortisol also negatively affects the immune system and prevents the release of immunotransmitters. Interference from other brain regions (e.g. hippocampus and amygdala) can also modify the HPA axis, as can neuropeptides and neurotransmitters.

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