Biomedical subjects

Michael Harbuz

Publications and source records attributed to Michael Harbuz.

4 recordsLinked to original sources

PubMed2003

Neuroendocrine-immune interactions.

Over the past 15 years, the mechanisms by which the brain communicates with the immune system and the immune system with the brain have been elucidated. Increasingly, we are beginning to realize that cytokines within the brain are no scientific oddity, but rather are an important component of normal brain functioning. They are able to alter behaviour, memory, stress responses, brain injury and are increasingly being linked to psychiatric disorders. Hormones, peptides and neurotransmitters regulate the immune system. Understanding the complex interactions of these systems is a challenge for the 21st century.

Animals↗

PubMed2002

Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis.

We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.

Adrenocorticotropic Hormone↗

PubMed2002

Neuroendocrinology of autoimmunity.

The HPA axis is fundamental for long-term survival and protection from the ravages of autoimmune disease. Continuing investigations suggest that the hypothesis linking susceptibility to autoimmune disease and a hyporesponsive HPA axis is somewhat simplistic. Instead, data from a number of different human diseases and from preclinical studies in a variety of models have suggested a more complicated picture. Alterations in the diurnal rhythms of ACTH, cortisol, and immune parameters appear to be linked to severity of disease. The use of low doses of steroids timed to target disrupted diurnal immune system changes in patients with RA may reduce the unfortunate side effects of long-term steroid use. Studies in cancer patients have related alterations in diurnal cortisol to survival. Whether differences in individual cortisol profiles are predictive of a deterioration in symptoms of autoimmune disease remains to be established. Responsiveness of the HPA axis to subtle challenges such as the dexamethasone suppression test and the related dexamethasone-CRF test suggest that there are different sub-populations of patients with RA and MS and these may have confounded earlier, apparently contradictory, studies. These different responses may be related to the severity of the disease. That these HPA axis differences can be altered beneficially through the use of antidepressants, as has been shown in MS, may impact on future health care strategies. However, reports of negative developments in arthritis associated with SSRI use suggest that the SSRIs may be unsuitable under some circumstances. The link of behavioral differences to alterations in neurotransmitter changes associated with disease is intriguing and opens new avenues of research. These future studies will require input from neuroscientists, neuroendocrinologists, psychologists, and immunologists working with the clinical specialties already involved in treating patients with autoimmune disease. These multidisciplinary studies reflecting the increased importance of hormonal and neurotransmitter involvement with the immune system hold great promise for the future.

Animals↗

PubMed2002

Neuroendocrine function and chronic inflammatory stress.

The factors regulating susceptibility and severity of autoimmune diseases are poorly understood. That neuroendocrine factors are critical modulators in this regard is self-evident. For example, there are major gender differences in susceptibility with women at greater risk than men of, for example, rheumatoid arthritis (RA) and multiple sclerosis (MS). The hypothalamo-pituitary-adrenal (HPA) axis has rightly attracted a considerable amount of attention. Of particular interest has been the hypothesis that susceptibility to autoimmune disease may be related to an impaired responsiveness of the HPA axis; that is, an inability to mount an appropriate cortisol response with which to down-regulate the immune system might allow the immune system to rampage unchecked and attack self. This hypothesis links regulation of the release from the adrenal gland of the potent anti-inflammatory glucocorticoids to the disease process. Endogenous glucocorticoids are crucial for the regulation of the severity of the disease process. The hypothesis proposing a link between a hyporesponsive HPA axis and susceptibility to disease is compelling. However, evidence from a number of sources has suggested that this may not be the entire story and alterations in the activity of the HPA axis have not been consistently observed in patients with RA. This review will concentrate on recent findings concerning the HPA axis in determining susceptibility to, and in regulating the severity of, inflammatory processes in autoimmune disease. These studies have revealed that a single exposure to endotoxin can confer protection to subsequent development of inflammation in an arthritis model in both neonatal and adult rats. Behavioural differences within a single population of rats are associated with differences in the plasma corticosterone responses to stress. However, relative hyporesponsiveness is not reflected by an increase in the severity of inflammation. In humans with RA the dexamethasone-corticotrophin-releasing factor (CRF) test has revealed two distinct sub-populations of patients. Studies in patients with MS have shown that this is not related to depression but rather to the severity of the disease. A better understanding of these complex neuroendocrine interactions may lead to novel clinical interventions.

Animals↗