Freda G. DeKeyser

Activation of the Adrenocortical Axis by Surgical Stress: Involvement of Central Norepinephrine and Interleukin-1

In the present study, we examined the mechanisms involved in the activation of the adrenocortical axis following surgical stress. Adult male rats underwent surgical laparotomy or craniotomy under ether anesthesia while control rats were only ether-anesthetized. Four hours following laparotomy or craniotomy, serum adrenocorticotropin (ACTH) and corticosterone (CS) were significantly increased and returned to almost basal levels after 24 h. Laparotomy also caused a significant depletion of corticotropin-releasing hormone (CRH-41) in the median eminence (ME). Pretreatment with dexamethasone 50 μg/kg completely abolished the pituitary-adrenal response while pretreatment with type II corticosteroid receptor antagonist caused a significant hypersecretion of both ACTH and CS and inhibited the effect of dexamethasone. The response to laparotomy was markedly attenuated in rats injected with 6-hydroxydopamine into the paraventricular nucleus (PVN) which significantly depletes norepinephrine (NE) PVN content. Intracerebroventricular injection of interleukin-1 receptor antagonist (IL-1ra) also inhibited the pituitary-adrenal response to laparotomy. The results suggest that (1) surgical stress activates the hypothalamo-pituitary-adrenal (HPA) axis via a mechanism which involves the release of CRH from the ME and NE input to the PVN; (2) the adrenocortical response is sensitive to the negative feedback of glucocorticoids via the mediation of type II glucocorticoid receptors, and (3) central IL-1 may be a mediator in the HPA axis response to surgical stress.

Psychoneuroimmunology in Critically Ill Patients

Psychoneuroimmunology is the study of the interactions among behavior, neural, and endocrine functions and the immune system. The purpose of this review is to briefly summarize the evidence concerning interactions among behavior, the neuroendocrine system, and the immune system, and to show how this evidence relates to critical care patients. It has been shown that the immune function of many patients in the intensive care unit is suppressed as a result of trauma, sepsis, or profound physiologic and psychological stress. Three of the most common stressors among patients in the intensive care unit are pain, sleep deprivation, and fear or anxiety. Findings have shown each of these stressors to be associated with decreased immune functioning. Nurses have an important responsibility to protect their patients from infection and promote their ability to heal. Several actions are suggested that can help the nurse achieve these goals. It is hoped that nurses would keep these interactions in mind while caring for their patients in the intensive care unit.

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary–adrenal axis: Attenuation by preemptive analgesia and by central amygdala lesion

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Effect of Exogenous Nitric Oxide and Inhibitors of Nitric Oxide Synthase on the Hypothalamic Pituitary Adrenal Axis Responses to Neural Stimuli

It has been shown that the hypothalamic-pituitary-adrenal (HPA) axis responses to immune-derived stimuli in particular can be modulated by nitric oxide (NO). In the present study we examined the effect of endogenous and exogenous NO on the HPA axis responses to neural stimuli which are not related to immune functions. Intracerebroventricular injection of NOR-3, a donor of NO, had no effect on basal HPA axis activity but significantly attenuated the secretion of median eminence (ME) CRH-41 as well as the serum ACTH and corticosterone (CS) in response to acute photic stimulation in a dose-dependent manner. Intracerebroventricular administration of N-ω-nitro-L-arginine methyl ester (L-NAME), a general NOS inhibitor, significantly enhanced ACTH and CS responses to this stress but did not change the basal levels of these hormones. On the other hand, i.c.v. injection of aminoguanidine, an inhibitor of inducible NO synthase (NOS) but not of neuronal NOS, did not affect the HPA axis responses to photic stimulation. These results suggest that: (1) NO is involved in modulation of the HPA axis responses to neural stimuli which are not dependent on immune factors, (2) the effect of NO is mediated by inhibition of hypothalamic ME CRH-41 secretion, and (3) this effect is probably mediated by neuronal NOS and not by inducible NOS.

Patients voice issues of dress and address.

Establishing a positive patient care environment is one of the most basic concepts of health care professional practice. Dress and personal address are aspects of this environment that are influenced by culture and express mutual respect within the patient-provider relationship. The Patient Sensitivity Questionnaire was administered to determine how 76 Israeli inpatients perceived forms of address and dress in their health care environment. Patients preferred that their health care providers wear formal dress and be addressed by their formal titles. Respondents did not object to being addressed by their first names. Based on these results, it would seem that this Israeli sample preferred to retain the traditional provider-patient environment.

The Involvement of Glucocorticoids and Interleukin-1 in the Regulation of Brain Prostaglandin Production in Response to Surgical Stress

Background: This study examined the role of glucocorticoids (GC) and interleukin-1 (IL-1) in regulating the production of brain prostaglandin E2 (PGE2) in response to surgical stress. Methods: Surgical stress was induced in rats by laparotomy or exploration of the carotid. PGE2 ex vivo production was measured in the frontal cortex or central amygdala of adrenalectomized rats, or of rats treated with either the GC type II receptor blocker (RU38486) or synthetic GC (dexamethasone). IL-1 involvement in mediating PGE2 response to surgical stress was examined in IL-1 receptor type I deficient (IL-1rKO) mice. Results: Surgical stress elevated serum corticosterone and increased PGE2 production by the frontal cortex and the central amygdala. A more pronounced PGE2 response was found in adrenalectomized rats and in rats treated with RU38486, whereas administration of dexamethasone inhibited stress-induced PGE2 production. IL-1rKO mice exhibited lower PGE2 production in the frontal cortex under basal condition and failed to increase PGE2 production in response to surgical stress. Conclusions: Surgical stress-induced production of brain PGE2 is specifically regulated by GC via the mediation of type II corticosteroid receptors. Normal IL-1 signaling is required for the production of brain PGE2 under basal conditions and in response to surgical stress.

Interactions of ACTH and TGFβ on monocyte proliferation: Implications for trauma and burn patients

The purpose of this study was to try to elucidate a possible biobehavioral mechanism associated with decreased immune function in trauma patients by determining whether there is an interaction between the effects of ACTH, a stress hormone, and TGF beta, a cytokine, on peripheral blood lymphocyte proliferation. Peripheral mononuclear lymphocytes (PMLs) from healthy donors were preincubated with varying concentrations of ACTH for 24 hr, stimulated with concanavalin A and increasing concentrations of TGF beta, and incubated for 72 hr. Proliferation was assayed by tritiated thymidine incorporation. A parallel aliquot of PMLs were incubated in the presence of ACTH to determine the direct effect of ACTH on mononuclear cell TGF beta production. While harvested supernatant from cells incubated in the presence of ACTH did not contain any detectable TGF beta, ACTH as well as TGF beta were found to significantly decrease cellular proliferation independent of one another. An even greater decrease in cellular proliferation was found when both ACTH and TGF beta were used, compared to either ACTH or TGF beta alone. These results suggest a biobehavioral interaction between ACTH and TGF beta at the cellular level and that interactions to relieve stress may assist in improving function and recovery from trauma.

The effects of stress, anxiety and depression on markers of peritoneal immune function in capd patients: An exploratory study

Abstract The purpose of this descriptive, correlational study was to explore the relationship between Stress. anxiety and depression and markers of peritoneal immune function in patients receiving Continuous Ambulatory Peritoneal Dialysis (CAPD). Thirty two subjects aged 30–77 years of whom 20 were male and 12 female and who were on CAPD for a mean of 25.3 months participated in the study. An overnight dialysis effluent exchange was used to measure peritoneal immune function. The markers were unstimulated (baseline) and stimulated (with phorbol ester) peritoneal cellular respiratory burst activity, number of peritoneal effluent macrophages, and effluent concentrations of PGE2 and IgG. Stress was measured with the Dialysis Stressor Scale and the Daily Hassles Questionnaire. Anxiety was measured using the State Trait Anxiety Inventory while depression was measured with the Self-Rating Depression Scale. Significant positive correlations were found between stimulated and unstimulated respiratory burst activit...