The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects

Dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) inhibit T-helper lymphocyte type 2 immune reactions and exert anti-inflammatory effects in some chronic inflammatory diseases. Both DHEA and, in particular, DHEAS levels are dramatically decreased in chronic inflammatory diseases whereas cortisol levels remain stable or are elevated. However, the time course of cortisol relative to DHEA production is not known. We tested whether administration of endotoxin to healthy male subjects can induce an early predominance of cortisol relative to DHEA and DHEAS. It is demonstrated that endotoxin induces a dose-dependent increase of cortisol in relation to DHEA (no effect at 0.2 ng endotoxin/kg body weight (b.w.), clear effect at 0.4 and 0.8 ng/kg b.w., p<0.05) and DHEAS (tested at 0.4 ng/kg b.w., P=0.014). The increase of cortisol relative to DHEA appears 4 h after endotoxin injection and 2 h after a strong increase of interleukin (IL)-6 relative to tumour necrosis factor (TNF). In addition, an increase of cortisol relative to 17OH-progesterone was observed. The ratio of serum IL-6/TNF was positively correlated with the ratio of serum cortisol/DHEA (R(Rank)=0.472, P=0.041) and serum cortisol/17OH-progesterone (R(Rank)=0.514, P=0.048). In conclusion, dissociation of cortisol relative to DHEA, DHEAS or 17OH-progesterone appears very early during a systemic inflammatory response which is associated with an increase of IL-6 relative to TNF. As in chronic inflammatory diseases, during an acute inflammatory response with endotoxin, these physiological hormone changes are probably necessary to achieve adequate cortisol levels at the expense of adrenal androgens.

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Techniques to Study Inflammasome Activation and Inhibition by Small Molecules

Molecules ◽

10.3390/molecules26061704 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1704

Author(s):

Diego Angosto-Bazarra ◽

Cristina Molina-López ◽

Alejandro Peñín-Franch ◽

Laura Hurtado-Navarro ◽

Pablo Pelegrín

Keyword(s):

Inflammatory Response ◽

Small Molecules ◽

Mechanism Of Action ◽

Inflammatory Diseases ◽

Inflammasome Activation ◽

Chronic Inflammatory Diseases ◽

Anti Inflammatory ◽

Inhibitory Molecules ◽

Inflammasome Inhibitors

Inflammasomes are immune cytosolic oligomers involved in the initiation and progression of multiple pathologies and diseases. The tight regulation of these immune sensors is necessary to control an optimal inflammatory response and recover organism homeostasis. Prolonged activation of inflammasomes result in the development of chronic inflammatory diseases, and the use of small drug-like inhibitory molecules are emerging as promising anti-inflammatory therapies. Different aspects have to be taken in consideration when designing inflammasome inhibitors. This review summarizes the different techniques that can be used to study the mechanism of action of potential inflammasome inhibitory molecules.

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Estimation of the inter- and intrasubject variability of the diurnal serum cortisol rhythm in healthy male subjects to evaluate the biomarker potential for drug target engagement

International Journal of Clinical Pharmacology and Therapeutics ◽

10.5414/cp202181 ◽

2015 ◽

Vol 53 (03) ◽

pp. 199-205

Author(s):

Fanni Natanegara ◽

Adrienne Tran ◽

Stephen Lowe ◽

Lai San Tham ◽

Christopher Chen

Keyword(s):

Drug Target ◽

Serum Cortisol ◽

Target Engagement ◽

Healthy Male ◽

Intrasubject Variability ◽

Male Subjects

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Concurrent Training Decreases Cortisol but Not Zinc Concentrations: Effects of Distinct Exercise Protocols

Scientifica ◽

10.1155/2016/7643016 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Guilherme Rosa ◽

Marcos de Sá Rego Fortes ◽

Danielli B. de Mello

Keyword(s):

Strength Training ◽

Serum Zinc ◽

Serum Cortisol ◽

Concurrent Training ◽

Zinc Status ◽

Study Session ◽

Zinc Concentrations ◽

Cortisol Levels ◽

Male Subjects ◽

Blood Variables

Objectives. To investigate the effects of distinct concurrent training (CT) protocols on zinc and cortisol concentrations and test the correlation between these blood variables.Methods. Samples of serum zinc and cortisol were assessed from 10 male subjects (27.1±4.8years old; BMI25.38±0.09) before and immediately after each study session: control (CS = no exercises), concurrent training 1 (CT1 = indoor cycling + strength training), and concurrent training 2 (CT2 = strength training + indoor cycle) with five days of interval between each.Results. There were no significant changes in zinc concentrations after the CS (Δ% = 8.45;p=0.07), CT1 (Δ% = 4.77;p=0.49), and CT2 (Δ% = −2.90;p=0.12) sessions. Cortisol levels showed significant decrease after CS (Δ% = −6.02;p=0.00), CT1 (Δ% = −26.32;p=0.02), and CT2 (Δ% = −33.57;p=0.05) sessions. There was a significant correlation between the variables only at CS (zinc post versus cortisol pre:r=0.82and cortisol post:r=0.82).Conclusions. CT decreases cortisol concentrations regardless of the sequence performed. No changes were found in zinc concentrations after the study sessions. The reduction in serum cortisol concentrations appear to occur by a mechanism independent of the zinc status.

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Endogenous galectins and the control of the host inflammatory response

Journal of Endocrinology ◽

10.1677/joe-08-0512 ◽

2009 ◽

Vol 201 (2) ◽

pp. 169-184 ◽

Cited By ~ 56

Author(s):

Lucy V Norling ◽

Mauro Perretti ◽

Dianne Cooper

Keyword(s):

Drug Discovery ◽

Inflammatory Response ◽

Inflammatory Diseases ◽

Molecular Targets ◽

Innovative Drug ◽

New Era ◽

Chronic Inflammatory Diseases ◽

Endogenous Lectins ◽

Anti Inflammatory ◽

Host Inflammatory Response

A new era of research is being devoted to deciphering endogenous mediators and mechanisms that are in place to resolve the inflammatory response. Accruing evidence indicates that galectins fall into this category of immunoregulatory mediators signifying their use as prospective novel anti-inflammatory agents. The focus of this review is to depict the immunoregulatory bioactivities of three members of the galectin superfamily, Galectin (Gal)-1, Gal-3 and Gal-9. Emphasis is given to the studies investigating the properties of these endogenous lectins. Gal-1, Gal-3 and Gal-9 are emerging as pertinent players in the modulation of acute and chronic inflammatory diseases, autoimmunity and cancer, and thus being increasingly recognised as molecular targets for innovative drug discovery.

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