Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 25
Filter
1.
Lancet Diabetes Endocrinol ; 10(3): 221-230, 2022 03.
Article in English | MEDLINE | ID: covidwho-1665596

ABSTRACT

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men. In this Personal View, we discuss how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19. Due to its role in the severity and progression of SARS-CoV-2 infections, we argue that sexual dimorphism has potential implications for disease treatment, public health measures, and follow-up of patients predisposed to the development of long COVID. We suggest that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID-19 to help to achieve better disease stratification and improved outcomes.


Subject(s)
COVID-19 , Health Status Disparities , Sex Characteristics , COVID-19/complications , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Hypothalamo-Hypophyseal System , Male , Pituitary-Adrenal System , Public Health
2.
Trials ; 23(1): 4, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1606541

ABSTRACT

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.


Subject(s)
COVID-19 , Shock, Cardiogenic , Adult , Humans , Hypothalamo-Hypophyseal System , Multicenter Studies as Topic , Pituitary-Adrenal System , Randomized Controlled Trials as Topic , SARS-CoV-2 , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/drug therapy , Treatment Outcome
3.
Med Sci (Paris) ; 37(11): 1047-1054, 2021 Nov.
Article in French | MEDLINE | ID: covidwho-1585739

ABSTRACT

Hypothalamus stimulation by inflammatory and / or stress signals can trigger activation of the HPA (hypothalamic-pituitary-adrenal) axis, which includes the hypothalamus, pituitary and adrenal gland. Acute activation of the HPA axis is fundamental for the fight or flight response. It allows a maximal energy mobilization available for an effort, whilst erasing fatigue. On the contrary, the chronic activation of this axis decreases muscle efficiency and leads to chronic fatigue. In this second part of our review will be discussed several strategic points that need to be considered for attempting to understand and treat together inflammation and chronic fatigue.


TITLE: Mécanismes sous-jacents à la fatigue chronique, un symptôme trop souvent négligé - II. De l'immunité dérégulée à la neuroinflammation et ses conséquences. ABSTRACT: L'activation de l'hypothalamus par des signaux inflammatoires et/ou de stress peut déclencher celle de l'axe HPA (hypothalamic-pituitary-adrenal axis), qui intègre l'hypothalamus, l'hypophyse et la glande surrénale. L'activation aiguë de l'axe HPA est fondamentale pour la réponse fight or flight (« combats ou fuis ¼). Elle permet de mobiliser un maximum d'énergie pour un effort, tout en effaçant la fatigue. En revanche, son activation chronique diminue l'efficacité musculaire et entraîne une fatigue chronique. On discutera dans cette partie de plusieurs points stratégiques à considérer pour tenter de comprendre et de traiter ensemble inflammation et fatigue chroniques.


Subject(s)
Fatigue Syndrome, Chronic , Hypothalamo-Hypophyseal System , Fatigue Syndrome, Chronic/etiology , Humans , Pituitary Gland , Pituitary-Adrenal System
4.
Intensive Care Med ; 46(12): 2284-2296, 2020 12.
Article in English | MEDLINE | ID: covidwho-1451948

ABSTRACT

Current literature addressing the pharmacological principles guiding glucocorticoid (GC) administration in ARDS is scant. This paucity of information may have led to the heterogeneity of treatment protocols and misinterpretation of available findings. GCs are agonist compounds that bind to the GC receptor (GR) producing a pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GR. We updated the meta-analysis of randomized trials investigating GC treatment in ARDS, focusing on treatment protocols and response. We synthesized the current literature on the role of the GR in GC therapy including genomic and non-genomic effects, and integrated current clinical pharmacology knowledge of various GCs, including hydrocortisone, methylprednisolone and dexamethasone. This review addresses the role dosage, timing of initiation, mode of administration, duration, and tapering play in achieving optimal response to GC therapy in ARDS. Based on RCTs' findings, GC plasma concentration-time profiles, and pharmacodynamic studies, optimal results are most likely achievable with early intervention, an initial bolus dose to achieve close to maximal GRα saturation, followed by a continuous infusion to maintain high levels of response throughout the treatment period. In addition, patients receiving similar GC doses may experience substantial between-patient variability in plasma concentrations affecting clinical response. GC should be dose-adjusted and administered for a duration targeting clinical and laboratory improvement, followed by dose-tapering to achieve gradual recovery of the suppressed hypothalamic-pituitary-adrenal (HPA) axis. These findings have practical clinical relevance. Future RCTs should consider these pharmacological principles in the study design and interpretation of findings.


Subject(s)
Glucocorticoids , Respiratory Distress Syndrome , Humans , Hypothalamo-Hypophyseal System , Methylprednisolone , Pituitary-Adrenal System , Respiratory Distress Syndrome/drug therapy
5.
Contemp Clin Trials ; 111: 106616, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487636

ABSTRACT

Opioid Use Disorders (OUDs) and drug overdose deaths are increasing at alarmingly high rates in the United States. Stress and dysregulation in biologic stress response systems such as the hypothalamic-pituitary-adrenal axis and noradrenergic system appear to play an important role in the pathophysiology of substance use disorders and relapse to drug use, particularly for women. Alpha-2 adrenergic agonist medications effectively decrease noradrenergic activity and have demonstrated benefit in preventing relapse to substance use and decreasing stress-reactivity and craving in cocaine- and nicotine-dependent women, compared to men. Alpha-2 adrenergic agonists may help decrease stress reactivity in individuals with OUDs and prevent relapse to drug use, but gender differences have yet to be systematically explored. We describe the rationale, study design and methodology of a randomized, double-blind, placebo-controlled clinical trial examining gender differences in stress, craving and drug use among adult men and women with OUD taking methadone or buprenorphine and randomly assigned to an alpha-2 adrenergic agonist, lofexidine, compared to placebo. In addition, we describe methods for measuring daily stress, craving and drug use in participant's natural environment as well as participant's physiological (i.e., heart rate, cortisol) and psychological (i.e., stress, craving) response to laboratory social and drug cue stressors. Lastly, we detail methods adopted to sustain research activity while following guidelines for the COVID-19 pandemic. ClinicalTrials.gov Registration Number: NCT03718065.


Subject(s)
Analgesics, Opioid , COVID-19 , Clonidine/analogs & derivatives , Craving , Humans , Hypothalamo-Hypophyseal System , Pandemics , Pituitary-Adrenal System , Recurrence , SARS-CoV-2
6.
Int J Mol Sci ; 22(21)2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1480799

ABSTRACT

The hypothalamus-pituitary-adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).


Subject(s)
COVID-19/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/virology , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/virology , Receptors, Glucocorticoid/metabolism , Critical Illness , Glucocorticoids/metabolism , Humans , Stress, Physiological
7.
Int J Mol Sci ; 22(15)2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1344938

ABSTRACT

Adaptation of organisms to stressors is coordinated by the hypothalamic-pituitary-adrenal axis (HPA), which involves glucocorticoids (GCs) and glucocorticoid receptors (GRs). Although the effects of GCs are well characterized, their impact on brain adaptation to hypoxia/ischemia is still understudied. The brain is not only the most susceptible to hypoxic injury, but also vulnerable to GC-induced damage, which makes studying the mechanisms of brain hypoxic tolerance and resistance to stress-related elevation of GCs of great importance. Cross-talk between the molecular mechanisms activated in neuronal cells by hypoxia and GCs provides a platform for developing the most effective and safe means for prevention and treatment of hypoxia-induced brain damage, including hypoxic pre- and post-conditioning. Taking into account that hypoxia- and GC-induced reprogramming significantly affects the development of organisms during embryogenesis, studies of the effects of prenatal and neonatal hypoxia on health in later life are of particular interest. This mini review discusses the accumulated data on the dynamics of the HPA activation in injurious and non-injurious hypoxia, the role of the brain GRs in these processes, interaction of GCs and hypoxia-inducible factor HIF-1, as well as cross-talk between GC and hypoxic signaling. It also identifies underdeveloped areas and suggests directions for further prospective studies.


Subject(s)
Disease Resistance , Glucocorticoids/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypoxia, Brain/metabolism , Ischemic Preconditioning , Pituitary-Adrenal System/metabolism , Signal Transduction , Animals , Humans , Hypothalamo-Hypophyseal System/pathology , Hypoxia, Brain/prevention & control , Pituitary-Adrenal System/pathology
8.
J Clin Neurosci ; 91: 283-287, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1333598

ABSTRACT

The new coronavirus (COVID-19) has emerged now in the world as a pandemic. The SARS-CoV-2 infection causes variant common symptoms, such as dry cough, tiredness, dyspnea, fever, myalgia, chills, headache, chest pain, and conjunctivitis. Different organs may be affected by COVID-19, such as the respiratory system, gastrointestinal tract, kidneys, and CNS. However, the information about the COVID-19 infection in the CNS is insufficient. We do know that the virus can enter the central nervous system (CNS) via different routes, causing symptoms such as dizziness, headache, seizures, loss of consciousness, and depression. Depression is the most common disorder among all neurological symptoms following COVID-19 infection, although the mechanism of COVID-19-induced depression is not yet clear. The aim of the present study is to investigate the probable mechanisms of COVID-19-induced depression. The reasons for depression in infected patients may be due to social and pathological factors including social quarantine, economic problems, stress, changes in the HPA axis, inflammation due to the entry of proinflammatory cytokines into the CNS, production of inflammatory cytokines by microglia, mitochondrial disorders, damage to the hippocampus, and malnutrition. By evaluating different factors involved in COVID-19-induced depression, we have concluded that depression can be minimized by controlling stress, preventing the cytokine storm with appropriate anti-inflammatory drugs, and proper nutrition.


Subject(s)
COVID-19 , Depression/epidemiology , Depression/etiology , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , SARS-CoV-2
9.
Rev Endocr Metab Disord ; 23(2): 233-250, 2022 04.
Article in English | MEDLINE | ID: covidwho-1303352

ABSTRACT

Patients with endogenous or exogenous glucocorticoid (GC) excess exhibit a range of side effects, including an increased risk of infections. Via both mechanism, immune impairments and cardiometabolic concomitant diseases, patients with GC excess could be at increased risk for COVID-19. The impact on incidence and outcome of a SARS-CoV-2 infection in this population are not yet completely clear. This review aims to compile the data available to date and to discuss the existing literature on this topic. Further we highlight potential effects of SARS-CoV-2 on the hypothalamic-pituitary-adrenal axis as well as the influence of endogenous or exogenous GC excess on SARS-CoV-2 mRNA vaccination. There is growing evidence suggesting an increased risk of infection and severe outcome in patients with high-dose GC therapy after contracting SARS-CoV-2. The few data and case reports on patients with endogenous GC excess and SARS-CoV-2 infection point in a similar direction: chronic GC excess seems to be associated with an unfavorable course of COVID-19. Whether this is mainly a primary immune-mediated effect, or also triggered by the many GC-associated comorbidities in this population, is not yet fully understood. Patients with endogenous or exogenous GC excess should be considered as a vulnerable group during the SARS-CoV-2 pandemic. Regardless of the cause, vaccination and consistent surveillance and control of associated comorbidities are recommended.


Subject(s)
COVID-19 , Glucocorticoids , Glucocorticoids/adverse effects , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Risk Factors , SARS-CoV-2
10.
Säo Paulo med. j ; 139(4): 398-404, Jul.-Aug. 2021. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1288720

ABSTRACT

ABSTRACT BACKGROUND: Critical diseases usually cause hypercortisolemia via activation of the hypothalamic-pituitary-adrenal axis. OBJECTIVES: To investigate the relationship between serum total cortisol level and mortality among coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU), at the time of their admission. DESIGN AND SETTING: Prospective study developed in a pandemic hospital in the city of Şırnak, Turkey. METHODS: We compared the serum total cortisol levels of 285 patients (141 COVID-19-negative patients and 144 COVID-19-positive patients) followed up in the ICU. RESULTS: The median cortisol level of COVID-19-positive patients was higher than that of COVID-19 negative patients (21.84 μg/dl versus 16.47 μg/dl; P < 0.001). In multivariate logistic regression analysis, mortality was associated with higher cortisol level (odds ratio: 1.20; 95% confidence interval: 1.08-1.35; P = 0.001). The cortisol cutoff point was 31 μg/dl (855 nmol/l) for predicting mortality among COVID-19-positive patients (area under the curve 0.932; sensitivity 59%; and specificity 95%). Among the COVID-19 positive patients with cortisol level ≤ 31 μg/dl (79%; 114 patients), the median survival was higher than among those with cortisol level > 31 μg/dl (21%; 30 patients) (32 days versus 19 days; log-rank test P < 0.001). CONCLUSION: Very high cortisol levels are associated with severe illness and increased risk of death, among COVID-19 patients in the ICU.


Subject(s)
Humans , Hydrocortisone , COVID-19 , Pituitary-Adrenal System , Prospective Studies , SARS-CoV-2 , Hypothalamo-Hypophyseal System , Intensive Care Units
11.
Psychoneuroendocrinology ; 132: 105345, 2021 10.
Article in English | MEDLINE | ID: covidwho-1284482

ABSTRACT

Loneliness is associated with multiple forms of psychopathology in youth. However, we do not yet know how loneliness gets "under the skin" in ways that may impact the long-term health and development of early adolescents. In particular, loneliness may influence youths' patterns of diurnal cortisol, an index of hypothalamic-pituitary-adrenal (HPA) axis functioning and a central predictor of health across the lifespan. The current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, or COVID-19) pandemic represents a salient period in which to study the consequences of loneliness, as recent work has provided evidence that the physical-distancing measures put in place to contain the virus have resulted in greater loneliness, particularly among youth. Thus, the current study aimed to examine the prospective association between loneliness during the COVID-19 pandemic and diurnal cortisol in early adolescents. We found that greater loneliness was associated with higher levels of cortisol at waking and a blunted cortisol awakening response (CAR). These results held even when controlling for covariates that can influence diurnal trajectories of cortisol. Critically, this pattern of HPA-axis functioning increases risk for adverse mental and physical health outcomes across adolescence and into adulthood. This study is the first to examine the prospective association between loneliness and diurnal cortisol in early adolescence, and the first to identify mechanisms that contribute to biological markers of distress during the COVID-19 pandemic. Findings underscore the importance of developing and distributing strategies to mitigate feelings of loneliness among youth.


Subject(s)
COVID-19 , Circadian Rhythm , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Loneliness/psychology , Pituitary-Adrenal System/metabolism , Adolescent , Female , Humans , Hydrocortisone/analysis , Male , Pituitary-Adrenal Function Tests , SARS-CoV-2 , Saliva/chemistry
12.
Medicina (Kaunas) ; 57(6)2021 May 27.
Article in English | MEDLINE | ID: covidwho-1256605

ABSTRACT

The current COVID-19 pandemic has necessitated the need to find healthcare solutions that boost or support immunity. There is some evidence that high-velocity, low-amplitude (HVLA) controlled vertebral thrusts have the potential to modulate immune mediators. However, the mechanisms of the link between HVLA controlled vertebral thrusts and neuroimmune function and the associated potential clinical implications are less clear. This review aims to elucidate the underlying mechanisms that can explain the HVLA controlled vertebral thrust--neuroimmune link and discuss what this link implies for clinical practice and future research needs. A search for relevant articles published up until April 2021 was undertaken. Twenty-three published papers were found that explored the impact of HVLA controlled vertebral thrusts on neuroimmune markers, of which eighteen found a significant effect. These basic science studies show that HVLA controlled vertebral thrust influence the levels of immune mediators in the body, including neuropeptides, inflammatory markers, and endocrine markers. This narravtive review discusses the most likely mechanisms for how HVLA controlled vertebral thrusts could impact these immune markers. The mechanisms are most likely due to the known changes in proprioceptive processing that occur within the central nervous system (CNS), in particular within the prefrontal cortex, following HVLA spinal thrusts. The prefrontal cortex is involved in the regulation of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis and the immune system. Bi-directional neuro-immune interactions are affected by emotional or pain-related stress. Stress-induced sympathetic nervous system activity also alters vertebral motor control. Therefore, there are biologically plausible direct and indirect mechanisms that link HVLA controlled vertebral thrusts to the immune system, suggesting HVLA controlled vertebral thrusts have the potential to modulate immune function. However, it is not yet known whether HVLA controlled vertebral thrusts have a clinically relevant impact on immunity. Further research is needed to explore the clinical impact of HVLA controlled vertebral thrusts on immune function.


Subject(s)
COVID-19 , Manipulation, Spinal , Humans , Hypothalamo-Hypophyseal System , Pandemics , Pituitary-Adrenal System , SARS-CoV-2
13.
Pain Med ; 22(6): 1441-1464, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1174950

ABSTRACT

MYTH: Corticosteroid injection for the treatment of pain is known to decrease the efficacy of the adenovirus vector-based vaccines for COVID-19. FACT: There is currently no direct evidence to suggest that a corticosteroid injection before or after the administration of an adenovirus vector-based COVID-19 vaccine decreases the efficacy of the vaccine. However, based on the known timeline of hypothalamic-pituitary-adrenal axis suppression following epidural and intraarticular corticosteroid injections, and the timeline of the reported peak efficacy of the Janssen and AstraZeneca vaccines, physicians should consider timing an elective corticosteroid injection such that it is administered no less than 2 weeks prior to and no less than 2 weeks following a COVID-19 adenovirus vector-based vaccine dose, whenever possible. We emphasize the importance of risk/benefit analysis and shared decision making in determining the timing of corticosteroid injections for pain indications in relation to receipt of a COVID-19 vaccine given that patient-specific factors will vary.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adenoviridae/genetics , Adrenal Cortex Hormones , Humans , Hypothalamo-Hypophyseal System , Pain/drug therapy , Pituitary-Adrenal System , SARS-CoV-2
14.
Pituitary ; 24(2): 143-145, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1074463

ABSTRACT

PURPOSE: Side effects of the coronavirus disease 2019 (COVID-19) vaccines include pain at the injection site, fatigue, headache, myalgias, arthralgias, chills, and fever, all of which can be early indicators of an increased need for glucocorticoid replacement in patients with adrenal insufficiency. The Pituitary Society surveyed its membership to understand planned approaches to glucocorticoid management in patients with adrenal insufficiency who will receive a COVID-19 vaccine. METHODS: Members were asked to complete up to 3 questions regarding their planned approach for use of glucocorticoid replacement in patients with proven adrenal insufficiency. RESULTS: Surveys were sent to 273 members and 103 responded. Thirty-six percent plan to recommend that patients automatically increase glucocorticoid dosage with administration of the first vaccine injection. Of these, 84% plan to increase glucocorticoid dose on the day of vaccination, and 49% plan to increase glucocorticoid dose prior to vaccination. Of the 64% who do not plan to recommend automatic glucocorticoid dose increase with vaccine administration, 88% plan to increase the dose if the patient develops a fever, and 47% plan to increase the dose if myalgias and arthralgias occur. CONCLUSIONS: Most clinicians plan to maintain the current glucocorticoid dose with vaccine administration. The vast majority plan and to increase glucocorticoid dose in case of fever, and just under half in case of arthralgias and myalgias. These survey results offer suggested management guidance for glucocorticoid management in patients with adrenal insufficiency.


Subject(s)
Adrenal Insufficiency/drug therapy , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Glucocorticoids/therapeutic use , Adrenal Insufficiency/epidemiology , Adrenal Insufficiency/pathology , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/adverse effects , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Endocrinology/organization & administration , Endocrinology/standards , Humans , Hypothalamo-Hypophyseal System/drug effects , Pandemics , Pituitary Diseases/therapy , Pituitary-Adrenal System/drug effects , Practice Patterns, Physicians'/standards , SARS-CoV-2/immunology , Societies, Medical , Surveys and Questionnaires
15.
Mol Psychiatry ; 26(9): 5087-5096, 2021 09.
Article in English | MEDLINE | ID: covidwho-1065838

ABSTRACT

The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.


Subject(s)
Depression/metabolism , NF-kappa B , Receptors, Glucocorticoid , Animals , Brain/metabolism , Hypothalamo-Hypophyseal System/metabolism , Mice , NF-kappa B/metabolism , Pituitary-Adrenal System/metabolism , Receptors, Glucocorticoid/metabolism
16.
Endocr Pract ; 27(2): 83-89, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1002515

ABSTRACT

OBJECTIVE: To study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection. METHODS: Morning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease. RESULTS: The median morning cortisol level was 196 (31-587) nmol/L. It was <100 nmol/L in 8 patients (28.6%), <200 nmol/L in 14 patients (50%), and <300 nmol/L in 18 patients (64.3%). The corresponding ACTH values had a median of 18.5 ng/L (range 4-38 ng/L), and the ACTH level was <10 ng/L in 7 patients (26.9%), <20 ng/L in 17 patients (60.7%), and <30 ng/L in 23 patients (82.1%). The repeated testing on different days showed a similar pattern. Overall, if a cutoff level of <300 nmol/L is considered abnormal in the setting of acute disease, 9 patients (32%) had cortisol levels below this limit, regardless of whether the test was done only once (3 patients) or 3 times (6 patients). When the disease was more severe, the patients had lower cortisol and ACTH levels, suggesting a direct link between the COVID-19 infection and impaired glucocorticoid response. CONCLUSION: Unexpectedly, the adrenocortical response in patients with COVID-19 infection was impaired, and a significant percentage of the patients had plasma cortisol and ACTH levels consistent with central adrenal insufficiency.


Subject(s)
COVID-19 , Hypothalamo-Hypophyseal System , Adrenocorticotropic Hormone , Adult , Aged , Female , Humans , Hydrocortisone , Male , Middle Aged , Pituitary-Adrenal System , SARS-CoV-2
18.
Med Hypotheses ; 145: 110303, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-799149

ABSTRACT

Populations in areas with higher levels of air pollution both indoors and outdoors show increased mortality rates when infected with coronavirus disease 2019 (COVID-19). The association between air quality and COVID-19 is commonly attributed to the risk of transmission. Although controlled transmission is crucial, further investigation into air quality traits that contribute to the lethality of COVID-19 in infected persons enables risk stratification and optimization of the allocation of resources. There is a need for a valid basis for the proactive identification of indicators of COVID-19 severity in air quality that allow for the implementation of systematic environmental improvements aimed at preventing COVID-19 mortality. In this paper, chronic exposure to fine particulate matter (PM) is identified as a source of disrupted activation of the hypothalamic-pituitary-adrenal (HPA) axis; it is therefore, a contributable variable to COVID-19 mortality.


Subject(s)
Air Pollutants/adverse effects , COVID-19/epidemiology , COVID-19/etiology , Particulate Matter/adverse effects , COVID-19/physiopathology , Humans , Hypothalamo-Hypophyseal System , Immune System , Inflammation , Models, Theoretical , Pituitary-Adrenal System , Risk Assessment
20.
Zhongguo Zhen Jiu ; 40(8): 799-802, 2020 Aug 12.
Article in Chinese | MEDLINE | ID: covidwho-738155

ABSTRACT

The effect of acupuncture-moxibustion on respiratory system and systemic immune inflammatory response were reviewed to explore the possible role of neuroimmunomodulation in the control of inflammatory response and the effect mechanism of cholinergic anti-inflammatory pathway on coronavirus disease 2019 (COVID-19). Acupuncture-moxibustion could produce the local and systemic anti-inflammatory effect on COVID-19 through the activation of cholinergic anti-inflammatory pathway. Compared with humoral anti-inflammatory pathway, the neuronal anti-inflammatory pathway has earlier initiation, rapider action, and more localization, which play a more important role in the initial stage of inflammatory response. This may be an important basis for acupuncture-moxibustion intervention in the early stage of COVID-19. In addition to cholinergic anti-inflammatory pathway, acupuncture-moxibustion may also play an anti-inflammatory role in activating sympathetic nerve, hypothalamic-pituitary-adrenal axis and other neural anti-inflammatory pathways. How acupuncture-moxibustion play its role in stimulating the vagus nerve and sympathetic nerve in different periods of inflammatory response, and whether the effect is based on the selection of acupoints and the methods of stimulation, will be the research direction of the transformation from basic research to clinical research for acupuncture-moxibustion.


Subject(s)
Acupuncture Therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Moxibustion , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , Acupuncture Points , Betacoronavirus , COVID-19 , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL