Nicholas R.S. Hall

Immunological responses of breast cancer patients to behavioral interventions

This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre-post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p<.017), mixed lymphocyte responsiveness (MLR) (p<.001), concanavalin A (Con-A) responsiveness (p<.001), and the number of peripheral blood lymphocytes (PBL) (p<.01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions.

Immune System and Psychological Changes in Metastatic Cancer Patients Using Relaxation and Guided Imagery: A Pilot Study

Abstract This study was designed to investigate the hypothesis that relaxation and imagery can measurably influence immune responsiveness. The research sample was a group of adult cancer patients with metastatic disease. The subjects systematically engaged in relaxation and guided imagery exercises over one year while monthly samples of blood were drawn for study in a laboratory blind to their identity or specific clinical conditions. Although cortisol and white blood cell counts were not significantly changed, several measures of immune system function were found to be significantly elevated compared to baseline: PHA Mitogen (p<.02); CON-A Mitogen (p<.006); Mixed Lymphocyte Response (p<.03); Interleukin II (p<.03); Natural Killer Cell Activity (p<.01); Erythrocyte-Rosette Assay (p<.001); IgG (p<.01); IgM (p<.001). Several psychological measures also changed over the same period including increased aggression and internal locus of control. All immune and psychological changes paralleled the use of relaxat...

Interleukin-1β stimulates adrenocorticotropin and corticosterone release in 10-day-old rat pups

Interleukin-1 (IL-1) is a cytokine secreted in response to immunological challenge which has effects in many physiological systems in adult models. Among the central nervous system effects of IL-1 are its ability to alter sleep patterns, body temperature, and certain neuroendocrine parameters including the release of ACTH and corticosterone (B) in vivo. This study investigated the ability of IL-1 to induce ACTH and B release in 10-day-old rats. This age was chosen due to a well documented phenomenon, the stress hyporesponsive period (SHRP), in which rodents display a blunted pituitary-adrenal response to stressors during the first 2 postnatal weeks (postnatal days 3-14). Administration of IL-1 to rat pups during the SHRP resulted in robust ACTH and B increases. Data are discussed in terms of the site of action and ontogeny of negative feedback mechanisms in the hypothalamic-pituitary-adrenal axis.

Stress and Immunity in Humans: Modifying Variables

Publisher Summary A large number of variables capable of modifying either the stress response and/or the immune system have been identified. They can be divided into several categories including psychological, environmental, and behavioral variables. Behavioral interventions have the potential to act on either physiological or mental processes. This chapter focuses on the variables that are capable of modulating the effects of stressors on the human immune system. The categories of variables are numerous and complex. They include (1) biological and pharmacological factors, (2) structural and energetic interventions, (3) ethnomedical practices, (4) mind-body control, which would include guided imagery and hypnotherapy, and (5) lifestyle factors. The extent to which behavioral interventions might have efficacy based on the inherent properties of the intervention is sometimes difficult to determine. They exert a beneficial influence through those processes activated by the placebo phenomenon. Mind-body variables are correlated with health outcome in a number of different contexts.

Effects of exercise on immune functions of undernourished mice

Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response.

Psychosocial Interventions and Immune Function

This chapter discusses psychosocial interventions and immunity. The therapeutic effects of psychosocial intervention are dependent on a strong belief on the part of the subject that the intervention is going to have a beneficial outcome. The strength of ones belief in the efficacy of a protocol is not the only important ingredient in psychosocial interventions. Consequently, those interventions that involve relaxation, which would include guided imagery, prayer, and biofeedback, may work through an independent mechanism that serves to downregulate the anxiety-and stress-induced production of immunoregulatory hormones and signals from the sympathetic branch of the autonomic nervous system. Overstimulation of the sympathetic branch of the autonomic nervous system has been implicated in sudden cardiac death, which can be brought on by psychosocial stress. When attempting to understand the mechanism via which psychosocial interventions might modulate immunity, one must realize that the intervention strategy and how it is carried out and perceived by the individual may in turn be a partial reflection of the immunologic status of the individual. Just as there are bidirectional chemical pathways that link the brain with the immune system, there may well be bidirectional links between behavior and the immune system such that each can influence the other.

The effects of interleukin-1 receptor antagonist protein (IRAP) infusion following spinal cord transection in rats

A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.

Thymic regulation of the hypothalamic-pituitary-gonadal axis.

The thymus gland and the cells that it regulates produce a number of soluble factors that are capable of indirectly modulating the immune system via reproductive neuroendocrine circuits. Studies dating to the turn of the century were designed to evaluate the effects of partially purified thymic extracts in treating various reproductive disorders as well as changes in gonadal tissue weights. More recent studies have focused on the chemical nature of the factors responsible for regulating reproductive function. A number of factors have been described. These include thymosin beta 4 which has been found to stimulate the release of luteinizing hormone releasing hormone and luteinizing hormone (LH). Other factors such as interleukin-1 (IL-1) have been found to inhibit the release of these two peptides. IL-1 has also been found to alter the expression of LH receptors in rat granulosa cells. Certain interferons have been found capable of suppressing estrogen and progesterone release. While many of the studies have been carried out using adult animal models, there is increasing evidence that exposure to cytokines during early development can have long lasting if not permanent effects upon the reproductive axis. These and related topics are the subject of this review.

Increased production of tumor necrosis factor and interleukin 1 by peritoneal macrophages from severely undernourished mice: Lack of correlation with serum corticosterone

Abstract The effect of severe undernutrition on the production by peritoneal macrophages of the immunoregulatory cytokines, interleukin 1 (IL1) and tumor necrosis factor (TNF), was studied using a mouse model. IL1 production was measured using the D10(N4)M cell assay which, unlike assays previously used to measure IL1 in malnutrition, is not responsive to other macrophage cytokines, such as TNF and IL6. Production of both IL1 and TNF was elevated in mice undernourished such that they lost 25% of their initial weight. Serum corticosterone levels were also elevated in these animals. The lack of inhibition of cytokine production by corticosterone is further evidence that high glucocorticoid levels are not a major cause of immunodepression in severely undernourished mice.

Long-Term Effects of Neuroendocrine–Immune Interactions during Early Development

This chapter discusses long-term effects of neuroendocrine–immune interactions during early development. The immune system is modulated by the central nervous system (CNS). The chapter presents a study that demonstrated a structural link between the nervous system and the immune system by observing the innervation of lymphoid tissue by noradrenergic and peptidergic fibers. In addition to altering immune responsiveness through autonomic nervous system projections, the CNS modulates bodily defenses through neuroendocrine activity. Many hormones that are under the control of the brain are capable of potentiating or diminishing certain measures of immune performance. These measures range from alterations in tumor rejection in vivo to changes in cell-mediated or humoral immunity in vitro . In addition to its immunoregulatory, antiviral, and antiproliferative effects, interferon is capable of modulating the neuroendocrine activity. Interferon used in treating certain hormone-dependent cancers based on evidence that estradiol, progesterone, and thyroxine are suppressed in normal women after interferon administration and that the secretion of testosterone is diminished in Leydig cells in vitro after incubation with interferon.