Brooke A. Millar

Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep.

This review describes mechanisms of immune-to-brain and brain-to-immune signaling involved in mediating physiological sleep and altered sleep with disease. The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways. Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production. Cytokines produced by cells of the immune and nervous systems regulate sleep. Cytokines released by immune cells, particularly interleukin-1β and tumor necrosis factor-α, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function. In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury. Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep. The immune system’s ability to affect behavior has important implications for understanding normal and pathological sleep. Sleep disorders are commonly associated with chronic inflammatory diseases and chronic age- or stress-related disorders. The best studied are rheumatoid arthritis, fibromyalgia and chronic fatigue syndromes. This article reviews our current understanding of neuroimmune interactions in normal sleep and sleep deprivation, and the influence of these interactions on selected disorders characterized by pathological sleep.

Chronically reducing sympathetic activity in the spleen during middle age does not reverse the age-related increase in β-AR-stimulated cAMP production in splenocytes

complications (r = .52, p = .041). Greater depressive symptomatology and greater total mood disturbance were also significantly associated with the development of wound healing complications at the surgical site during hospitalization (r = .53, p = .041 and r = .53, p = .043, respectively). Although drawn from a modest sample size, these data suggest PNI factors may be associated with clinically significant outcomes among women who are hospitalized secondary to TAH-BSO for endometrial cancer. Our ongoing/future research will identify the relevant biobehavioral confounds in this population, as well as assess the efficacy of presurgical psychological interventions on acute postsurgical outcomes in this population.

135 EFFECTS OF AGING AND THE ANTIHYPERTENSIVE DRUG RILMENIDINE ON NERVE GROWTH FACTOR EXPRESSION IN THE SPLEEN OF MALE F344 RATS.

Previous research in our laboratory showed an age-related decline in noradrenergic (NA) sympathetic innervation of spleens from male Fischer 344 (F344) rats. Since nerve growth factor (NGF) plays an important role in determining the density of sympathetic innervation of target tissues throughout life, dysregulation of NGF expression in splenic target cells might explain the loss of sympathetic nerves. Moreover, chronically heightened sympathetic activity can also destroy nerve terminals by increased oxidative stress resulting from the breakdown of norepinephrine. The purpose of this study was to investigate whether these mechanisms are responsible for the age-related loss of splenic sympathetic nerves. Western blot analysis of NGF protein expression was evaluated in splenic lysates from untreated young (3 month) and old (18 month) male F344 rats and from 15-month-old rats treated with vehicle or rilmenidine (0.5 mg/kg and 1.5 mg/kg, bid [IP]) for 3 months to down-regulation of sympathetic activity. Our studies showed a 40% decrease in NGF protein levels in spleens from old rats compared with young adults. Noteworthy, rilmenidine induced a dose-dependent effect on NGF protein levels: administration of low and high doses of rilmenidine increased splenic NGF levels by 60 and 50%, respectively, compared with the vehicle group (sterile physiologic saline). Splenic NGF levels in the low-dose rilmenidine-treated group (500 μg/kg) were not different from those in 3-month-old F344 rats. Collectively, these findings support our hypothesis that changes in NGF protein expression might explain, at least in part, the age-related decline in sympathetic innervation of the spleen. Furthermore our data suggest that age-related changes in sympathetic activity in the spleen during middle age may precipitate the loss of NGF protein in spleens from old F344 male rats. This research is supported by NIH grant NS44032.

Effects of ageing and the antihypertensive drug rilmenidine on nerve growth factor (NGF) expression in the spleen of male F344 rats

ity to react to injury, might be of crucial importance as well. The purpose of this study was to investigate the changes in the expression of immune cells in the skin in relation to speed of wound healing and different psychological factors in humans. Twenty-two male non-smokers participated in this study. Every subject received a standard 4-mm punch biopsy. The healing process was monitored via ultrasound scanning, and the immune cells in the skin were analysed using different histological and immunohistochemical methods on the skin samples removed during the biopsy. Participants completed questionnaires on perceived stress, emotional distress, personality factors, and health behaviours 2 weeks prior, directly after and 2 weeks after the biopsy. The present study indicates the potential importance of the immune status of the skin as one of the possible pathways between psychological factors and wound healing. According to the present findings the level of activation of immune cells in the skin seems to be important in this process. Also, although in most of the analysis it failed to show statistically significant results, the expression of Langerhan’s cells deserves further investigation in this field. Macrophages showed no importance in this mechanism.

99 Immunization with KLH differentially affects splenic sympathetic activity in two strains of young and old rats

analysis of covariance, the preto post-intervention comparisons indicated that at post-intervention, those in the Tai Chi group had higher existential well-being (p 6 .01), higher perceptions of social support in the realm of guidance (p 6 .05), and more frequently used appraisal-focused coping strategies (p 6 .05). Immunological differences for the Tai Chi group included lower levels of TNF-a (p 6 .01) and higher levels of IL-2 (p 6 .05). Tai Chi practice entails several potentially therapeutic aspects. Learning to experience the world from a mindful, balanced perspective as well as exploring stress responses through meaningful meditative movement encourages proactive rather than reactive responses to perceived stress. Perhaps most importantly, altering perceptions of stressors and strengthening existential well-being along with the sense of available social support may be key components in ultimately impacting neuroendocrine-immune processes and health outcomes. Elevated levels of IL-2 may be associated with reduced physiological stress effects and enhanced cellular immunity overall, whereas reduction in levels of TNF-a may be related to decreased stimulation of the HPA axis and lowered induction of illness behaviors such as fatigue and depressed mood. Further examination of immune parameters will be needed to explain changes in cytokine patterns. However, it is possible that enhanced well-being and altered perceptions of stressors associated with Tai Chi training are causally related to such changes, as would be predicted in the psychoneuroimmunological framework.