Asnuntuck Community College

Cortisol is a prototypical human stress hormone essential for life, yet the precise role of cortisol in the human stress response to injury or infection is still uncertain. Glucocorticoids (GCs) such as cortisol are widely understood to suppress inflammation and immunity. However, recent research shows that GCs also induce delayed immune effects manifesting as immune stimulation. In this study, we show that cortisol enhances the immune-stimulating effects of a prototypical proinflammatory cytokine, interferon-υ (IFN-υ). We tested the hypothesis that cortisol enhances IFN-υ-mediated proinflammatory responses of human mononuclear phagocytes (monocyte/macrophages [MOs]) stimulated by bacterial endotoxin (lipopolysaccharide [LPS]). Human MOs were cultured for 18 hours with or without IFN-υ and/or cortisol before LPS stimulation. MO differentiation factors granulocyte-macrophage colony stimulating factor (GM-CSF) or M-CSF were added to separate cultures. We also compared the inflammatory response with an acute, 4-hour MO incubation with IFN-υ plus cortisol and LPS to a delayed 18-hour incubation with cortisol before LPS exposure. MO activation was assessed by interleukin-6 (IL-6) release and by multiplex analysis of pro- and anti-inflammatory soluble mediators. After the 18-hour incubation, we observed that cortisol significantly increased LPS-stimulated IL-6 release from IFN-υ-treated undifferentiated MOs. In GM-CSF-pretreated MOs, cortisol increased IFN-υ-mediated IL-6 release by >4-fold and release of the immune stimulant IFN-α2 (IFN-α2) by >3-fold, while suppressing release of the anti-inflammatory mediator, IL-1 receptor antagonist to 15% of control. These results were reversed by either the GC receptor antagonist RU486 or by an IFN-υ receptor type 1 antibody antagonist. Cortisol alone increased expression of the IFN-υ receptor type 1 on undifferentiated and GM-CSF-treated MOs. In contrast, an acute 4-hour incubation of MOs with IFN-υ and cortisol showed classic suppression of the IL-6 response to LPS. These results reveal a surprisingly robust proinflammatory interaction between the human stress response hormone cortisol and the immune activating cytokine IFN-υ. The results support an emerging physiological model with an adaptive role for cortisol, wherein acute release of cortisol suppresses early proinflammatory responses but also primes immune cells for an augmented response to a subsequent immune challenge. These findings have broad clinical implications and provide an experimental framework to examine individual differences, mechanisms, and translational implications of cortisol-enhanced immune responses in humans.

We track the trajectories of individual directed horocycles on the modular surface. Our tracking is constructive, and we thus effectively establish topological transitivity and even line-transitivity for the horocyclic flow.

practices pediatrics at Enfield Pediatric Associates, enfield, connecticut. He is the author of Patients Are a Virtue and a member of the JAAPA editorial board. Visit the author at http://briantmaurer.wordpress.com.Figure

Abstract Over half of the total diabetic population in the UK is over 65 years old and this presents particular challenges for therapeutic management. In this Expert Panel Discussion, the panel considers issues and solutions around prescribing for type 2 diabetes in elderly patients.

practices pediatrics at Enfield Pediatric Associates, Enfield, Connecticut. He is the author of Patients Are a Virtue and a member of the JAAPA editorial board. Visit the author at www.lulu.com/briantmaurer.

Résumé L’adoption a été longtemps idéalisée et soumise à une obligation de réussite, mais on constate aujourd’hui que la filiation adoptive ne va pas de soi. Les références habituelles font défaut. Les parents et les enfants doivent inventer des façons de tisser et de consolider des liens dont les professionnels ne mesurent pas toujours la complexité. La parentalité reste un vaste domaine à explorer dans le cadre de l’adoption.