PubMed · 4341516
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K Ernst. 1972-06-15. [Polymyositis].. https://pubmed.ncbi.nlm.nih.gov/4341516/
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Stress is known to either up or down regulate immunity. In this study, mice were subjected to handling combined with rectal temperature measurement (RTM) stress or handling only stress. We investigated whether there were any significant differences in the effect of handling combined with RTM and handling only on NK cell activity, serum cytokine (IL-1beta, IL-6, and TNF-alpha) and ACTH and beta-endorphin levels, and splenic cytokine (IL-1beta, IL-6, TNF-alpha, IFN-alpha, and IFN-beta) levels. Circulating cytokines and hormones and splenic cytokine mRNA levels were measured in individual mice. NK cell activity was significantly increased in both stress groups when compared to the control group. Handling combined with RTM produced significantly increased serum levels of IL-1beta, IL-6, and beta-endorphin. Serum IL-1beta, ACTH, and beta-endorphin were elevated significantly in the handling only group. Splenic TNFalpha mRNA in both of the stress groups and IL-6 mRNA in handling only group decreased significantly. Our observations are supported by existing literature demonstrating that various stressors have differential effects on immune functions and the neuroendocrine hormones and cytokines, which regulate them.
RATIONALE: It has been suggested that hypothalamic-pituitary-adrenocortical (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with antidepressants. Mirtazapine acts as an antagonist at presynaptic alpha(2)-receptors and at postsynaptic 5-hydroxytryptamine (5-HT)(2), 5-HT(3) and histamine H(1) receptors. It has been shown acutely to inhibit cortisol secretion in healthy subjects. OBJECTIVE: In this study, we investigated whether mirtazapine may downtune HPA axis hyperactivity in depressed patients and whether this is related to treatment outcome. METHODS: Forty patients suffering from a major depressive episode (DSM-IV criteria) were treated with mirtazapine for 5 weeks. The combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) was performed before and after 1 week of mirtazapine treatment (45 mg daily). RESULTS: Mirtazapine effectively reduced the overshoot of cortisol and ACTH during the DEX/CRH test both in treatment responders and non-responders within 1 week. CONCLUSIONS: Apparently, mirtazapine rapidly attenuates HPA axis hyperactivity in depressed patients via direct pharmacoendocrinological effects. However, this amelioration of HPA system dysregulation is not necessarily related to clinical improvement.
It is well established that the hypothalamic-pituitary-adrenal responses to immune stressors are sexually dimorphic in rodents (females > males), but the underlying mechanism is still unclear. To investigate the mechanism, in this study we examined whether the sex steroid environment affects the following variables in male and female rats: (1) plasma levels of ACTH, interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) after systemic lipopolysaccharide (LPS) administration; (2) static concentrations of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the mediobasal hypothalamus (MBH) and those of ACTH in the anterior pituitary (AP); and (3) the binding characteristics of IL-1beta, IL-6 and TNF-alpha in the MBH and AP. LPS-induced ACTH release was significantly higher in female than in male rats, and this sexual difference was abolished by performing gonadectomy in both sexes. Administration of physiological doses of testosterone and oestradiol to gonadectomized males and females, respectively, restored the altered ACTH responses to normal. Changes in the sex steroid milieu did not affect plasma cytokine responses to LPS, tissue contents of CRH, AVP and ACTH, or the IL-6 binding characteristics in the MBH and AP. However, the number of IL-1beta and TNF-alpha binding sites, but not their binding affinities, in the MBH showed significant changes according to altered sex hormone milieu, in the same direction as the LPS-induced ACTH response. These results suggest that the hypothalamic sensitivity to peripheral IL-1beta and TNF-alpha may be an important mechanism underlying the sexually dimorphic ACTH response to LPS in rats.