Effects of Systemic versus Local Administration of Corticosteroids on Mucosal Tolerance

Kerzerho, Jérôme; Wunsch, D.; Szely, Natacha; Meyer, Hellmuth-Alexander; Lurz, Lisa Caroline; Röse, Lars; Wahn, Ulrich; Akbari, Omid; Stock, Philippe

doi:10.4049/jimmunol.1101405

Cited by 15 publications

(11 citation statements)

References 42 publications

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“…The immunosuppressant and anti-inflammatory properties of corticosteroids are well established ( 45 , 46 ). A recent study ( 47 ) revealed that the systemic rather than the topical administration influences the mucosal tolerance. The authors concluded that the route of administration rather than the doses of corticosteroids administered affects the immune response, this finding being in agreement with our results.…”

Section: Discussionmentioning

confidence: 99%

Salivary concentration of the antimicrobial peptide LL-37 in patients with oral lichen planus

Davidopoulou

Theodoridis

Nazer

et al. 2014

Journal of Oral Microbiology

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BackgroundThe antimicrobial peptide LL-37 is a significant molecule of innate immunity and recent studies indicate that it plays an important role in maintaining oral health. Yet limited knowledge exists on its role in oral diseases and oral lichen planus (OLP) in particular.ObjectiveThe study aimed to examine: 1) the salivary concentration of LL-37 in patients with OLP and healthy subjects, 2) the relation between the type (reticular or erosive) and size of OLP lesions and LL-37 concentration, and 3) the effect of the therapeutic modalities on LL-37 levels.DesignThe salivary peptide concentration in samples from 20 patients and 30 healthy subjects at the same age range was determined by ELISA.ResultsDespite the wide variation in peptide concentration found in both groups, the healthy subjects exhibited significantly lower levels than patients. Patients with the erosive form had significantly higher peptide concentrations than patients with the reticular form. Systemic treatment with corticosteroids resulted in a significant decrease of the salivary peptide concentration, while other treatment modalities, such as administration of vitamins A and E or local application of corticosteroids had no effect. Improved clinical appearance of the lesions was followed by a decrease in the salivary LL-37 level.ConclusionsSalivary concentration of LL-37 correlates to the manifestation of mucosa lesions in OLP patients, the highest levels being observed in the most severe cases. This increase in peptide levels may protect against lesion infection and promote a quick wound healing.

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Section: Discussionmentioning

confidence: 99%

Salivary concentration of the antimicrobial peptide LL-37 in patients with oral lichen planus

Davidopoulou

Theodoridis

Nazer

et al. 2014

Journal of Oral Microbiology

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“…The administration of corticosteroids was reported to inhibit respiratory tolerance [43] and to permanently amplify the Th2 responses [44]. Dendritic cells from corticosteroid-treated mice have been shown to be unable to transfer respiratory tolerance or induce Treg cells [45]. Therefore, GC released upon stress exposure might bias immune regulation preferentially towards a Th2 response in response to a specific antigen, thereby eventually aggravating asthmatic responses to antigen challenges subsequent to stress exposure.…”

Section: Discussionmentioning

confidence: 99%

The Involvement of Glucocorticoids in Psychological Stress-Induced Exacerbations of Experimental Allergic Asthma

Okuyama

Dobashi

Miyasaka

et al. 2014

Int Arch Allergy Immunol

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Background: Psychological stress is associated with the aggravation of asthma symptoms. Glucocorticoids (GC), which are stress hormones released upon exposure to stress, have the potential to shift immune responses towards a predominant Th2 response by priming antigen-presenting cells to produce lower levels of IL-12 as well as reducing the development of regulatory T cells. However, the involvement of GC in psychological stress-induced exacerbations of allergic asthma has not yet been clarified. Methods: Sensitized mice were exposed to restraint stress followed by forced swimming stress, during which a GC receptor antagonist or a GC synthesis inhibitor was administered, and then antigen was inhaled. Corticosterone levels in the blood were measured in stressed and nonstressed mice. After antigen inhalation, the airway responses to aerosolized methacholine, epithelial mucus secretion and airway inflammation were evaluated, and the IL-13 contents in bronchoalveolar lavage fluid were measured. Results: The exposure to stress significantly increased corticosterone levels. Allergic airway responses and the increase of IL-13 contents evoked by antigen inhalation were significantly higher in stressed mice than in nonstressed mice. The administration of a GC receptor antagonist and a GC synthesis inhibitor during stress exposure significantly reduced the exacerbation of the airway responses and the increase of IL-13 contents in stressed mice challenged with antigen. Conclusions: These results indicate that the increased release of GC upon exposure to stress has a priming effect on the aggravation of allergic airway responses following the exposure, suggesting a pathophysiological role for the neuroendocrine axis in linking psychological stress to asthma exacerbations.

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“…In addition, GC treatment during antigen inhalation to promote the development of respiratory tolerance was shown to eliminate IL-10-producing dendritic cells, which are required for the development of IL-10-producing Treg cells, leading to Th2-biased sensitization and allergic airway responses upon antigen exposure (Stock et al 2005). Interestingly, the development of respiratory tolerance was shown to be prevented by systemic, but not local, GC administration (Kerzerho et al 2012), in accordance with our finding that respiratory tolerance was inhibited in mice that showed increased blood GC levels in response to stress exposure (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

Maternal Separation as Early-Life Stress Causes Enhanced Allergic Airway Responses by Inhibiting Respiratory Tolerance in Mice

Ouchi

Kawano

Yoshida

et al. 2018

Tohoku J. Exp. Med.

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Epidemiologic studies indicate that exposure to psychosocial stress in early childhood is a risk factor of adult-onset asthma, but the mechanisms of this relationship are poorly understood. Therefore, we examined whether early-life stress increases susceptibility to adult-onset asthma by inhibiting the development of respiratory tolerance. Neonatal BALB/c female mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA and the adjuvant aluminum hydroxide. Maternal separation (MS) was applied as an early-life stressor during the induction phase of immune tolerance. The mice were challenged with OVA aerosol in adulthood, and allergic airway responses were evaluated, including airway hyper-responsiveness to inhaled methacholine, inflammatory cell infiltration, bronchoalveolar lavage fluid levels of interleukin (IL)-4, IL-5, and IL-13, and serum OVA-specific IgE. We then evaluated the effects of MS on the development of regulatory T (Treg) cells in bronchial lymph nodes (BLN) and on splenocyte proliferation and cytokine expression. In mice that underwent MS and OVA tolerization, the allergic airway responses and OVA-induced proliferation and IL-4 expression of splenocytes were significantly enhanced. Furthermore, exposure to MS was associated with a lower number of Treg cells in the BLN. These findings suggest that exposure to early-life stress prevents the acquisition of respiratory tolerance to inhaled antigen due to insufficient Treg cell development, resulting in Th2-biased sensitization and asthma onset. We provide the evidence for inhibitory effects of early-life stress on immune tolerance. The present findings may help to clarify the pathogenesis of adult-onset asthma.

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Effects of Systemic versus Local Administration of Corticosteroids on Mucosal Tolerance

Cited by 15 publications

References 42 publications

Salivary concentration of the antimicrobial peptide LL-37 in patients with oral lichen planus

Salivary concentration of the antimicrobial peptide LL-37 in patients with oral lichen planus

The Involvement of Glucocorticoids in Psychological Stress-Induced Exacerbations of Experimental Allergic Asthma

Maternal Separation as Early-Life Stress Causes Enhanced Allergic Airway Responses by Inhibiting Respiratory Tolerance in Mice

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