Year: 2013
Type: article
Abstract: Stress is commonly considered to be immunosuppressive, but in some diseases states, such as asthma or infection, stress can be immunoenhancing.This immunoenhancement has been associated with immune cell glucocorticoid resistance that renders the cells insensitive to the anti-inflammatory effects of glucocorticoids.A unique murine social disruption stress paradigm, SDR, can model the stress-induced glucocorticoid resistance and exacerbation of inflammation, which can be relevant to inflammatory diseases in humans.In the context of SDR, stress enhances inflammation and delays resolution in an Aspergillus fumigatus (Af) allergic airway inflammation model.In stressed and Af challenged mice, gene expression data suggested increased inflammation (IL-1β, TNF-α, GM-CSF) with histological data supporting that the increase was due to infiltrating inflammatory cells.Furthermore, stress and Af challenge most prominently increased granulocytes in the lung compared to controls.Bone marrow chimeras demonstrated that the increase in immune cells was bone marrow-derived, and that stress induced myeloid progenitor cell egress and trafficking to lung.Closer examination of the granulocytic population identified many as neutrophilic populations.Using the antibodies to CD16 and CD49d, iii several distinct neutrophil populations were visualized including apoptotic, mature, activated, or immature neutrophils.Stress and Af challenge significantly increased the immature neutrophil population in both the lung and blood.In the clinic, it has been shown that a rapid release of immature neutrophils from the bone marrow can occur during times of stress and immune challenge.The consequences of this state of neutrophilia on disease are still being determined, but it is known these neutrophils have a higher capacity to induce inflammation and exacerbate patient symptoms.In a second study, we examined the consequences of Y1 receptor (Y1R), β-adrenergic receptor (βAR), and IL-1 receptor type 1 (IL-1R1) inactivation in a murine model of periodontal inflammation and stress-exacerbated inflammation.Previous studies show NPY, via Y1Rs, modulate NE that subsequently modulate cytokines like IL-1β via βARs.In turn, IL-1β modulates NPY and NE via IL-1R1 to precipitate inflammation.We antagonized the Y1R or βAR or used IL-1R1 knockout mice in the absence or presence of SDR.Porphyromonas gingivalis (P.gingivalis) or vehicle was injected into calvarial tissue of Y1R or βAR antagonized or IL-1R1 knockout non-stressed mice or SDR mice.After 24 hours, proinflammatory gene expression was determined.Y1R or βAR antagonisttreated P. gingivalis-infected mice had increased expression of proinflammatory cytokines compared to vehicle-treated P. gingivalis-infected mice.In non-infected animals, SDR increased proinflammatory gene expression as compared to iv control mice.In infected animals, SDR further exacerbated P. gingivalis-induced proinflammatory gene expression as compared to control animals, and this increase was abrogated by blocking Y1Rs and βARs during stress.IL-1R1 deficiency abrogated proinflammatory cytokine expression in non-stressed or stressed conditions.Altogether, the Y1R, βAR, and IL-1R1 are important mediators in inflammatory and stress-exacerbated inflammatory processes, thus elucidating potential mechanisms for the connection of stress to periodontal inflammation.Overall, stress enhances disease states such as allergic airway inflammation and periodontal inflammation through increased immune cell trafficking and through neuronal systems.
Author: Brenda F. Reader
Institution: The Ohio State University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2521503399