Glucocorticoids: mechanisms of action and anti‐inflammatory potential in asthma

Velden, Vincent van der

doi:10.1080/09629359890910

Cited by 172 publications

(107 citation statements)

References 156 publications

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“…Steroids, such as prednisolone, are powerful drugs that act at the genetic level resulting in the down-regulation of various proinflammatory mediators such as cytokines as well as immune pathways (35). These drugs, with nonspecific actions, possess numerous side effects, and their chronic use must be used with caution in patients (36,37).…”

Section: Discussionmentioning

confidence: 99%

A Potent Human C5a Receptor Antagonist Protects against Disease Pathology in a Rat Model of Inflammatory Bowel Disease

Woodruff¹,

Arumugam²,

Shiels³

et al. 2003

The Journal of Immunology

109

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The complement system is implicated in the pathogenesis of human inflammatory bowel disease, but the specific role of C5a has never been examined. We have compared the efficacy of an orally active human C5a receptor antagonist (AcPhe[Orn-Pro-d-cyclohexylalanine-Trp-Arg]), prednisolone, and infliximab against trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The drugs were administered either 2 days before or 24 h after TNBS instillation, and rats were then examined after 8 days. Drug-free colitis control rats showed severe disease pathology with significant mortality (39%). Rats pre or posttreated with the C5a antagonist (10 mg/kg/day peroral, 0.3 mg/kg/day s.c.) had reduced mortality and significantly improved macroscopic scores, colon edema, colon myeloperoxidase levels, reduced concentrations of TNF-α levels in the colon and serum, and had greater food intake resulting in greater weight gains than colitis-only rats. Rats pretreated with prednisolone (1 mg/kg/day s.c.) displayed significant improvement in parameters measured, but posttreatment was ineffective. Single dose pretreatment with the TNF-α inhibitor infliximab (3 mg/kg i.v.) also had significant improvements in the parameters measured. Rats pretreated with a combination of the C5a antagonist and prednisolone showed no greater improvements than either drug alone. These findings suggest a central role for complement, particularly C5a, in the pathology of TNBS-induced colitis in rats, indicating a possible therapeutic role for C5a antagonists in inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 99%

A Potent Human C5a Receptor Antagonist Protects against Disease Pathology in a Rat Model of Inflammatory Bowel Disease

Woodruff¹,

Arumugam²,

Shiels³

et al. 2003

The Journal of Immunology

109

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“…cortisone) are classically used in the clinical setting to decrease inflammatory responses (e.g. asthma, Van der Velden, 1998;rheumatoid arthritis, Gaffo et al, 2006), though recent research indicates they may have acute pro-inflammatory qualities as well, especially in response to injury (Sorrells and Sapolsky, 2007). Exogenous glucocorticoid administration decreases pro-inflammatory cytokine release, including TNF-α (Barnes, 1998), and glucocorticoid receptor blockade increases TNF-α levels (Roggero et al, 2006).…”

mentioning

confidence: 99%

Female temperament, tumor development and life span: Relation to glucocorticoid and tumor necrosis factor α levels in rats

Cavigelli

Bennett

Michael

et al. 2008

Brain, Behavior, and Immunity

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Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high-or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-α (TNF-α) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-α levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, highlocomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally-occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production.

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“…As corticosteroids suppress the recruitment and activation of inflammatory cells, inhibit the expression of cytokines and chemokines, and attenuate airway inflammation, these are the key drugs for the treatment of asthma regardless of the atopic status or the presence of specific IgE responses to allergens [1][2][3] . Most asthma patients can be well controlled with a low-to-moderate dose of inhaled corticosteroids.…”

mentioning

confidence: 99%

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

et al. 2013

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Type-2 innate immune responses that occur in airways and are accompanied by goblet-cell hyperplasia and mucus production are largely driven by interleukin-33 (IL-33) and natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2s) and the major target of IL-33. Here we report that the corticosteroid resistance observed as a result of airway inflammation triggered by sensitization and exposure to allergen is induced via the IL-33/NHcell axis. Thymic stromal lymphopoietin (TSLP) synthesized during airway inflammation plays a pivotal role in the induction of NH-cell corticosteroid resistance in vitro and in vivo, by controlling phosphorylation of STAT5 and expression of Bcl-xL in NH cells. Blockade of TSLP with a neutralizing antibody or blocking the TSLP/STAT5 signalling pathway with low molecular-weight STAT5 inhibitors such as pimozide restores corticosteroid sensitivity. Thus, the TSLP-STAT5 pathway could be a new therapeutic target in severe, corticosteroid-resistant asthma.

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Glucocorticoids: mechanisms of action and anti‐inflammatory potential in asthma

Cited by 172 publications

References 156 publications

A Potent Human C5a Receptor Antagonist Protects against Disease Pathology in a Rat Model of Inflammatory Bowel Disease

A Potent Human C5a Receptor Antagonist Protects against Disease Pathology in a Rat Model of Inflammatory Bowel Disease

Female temperament, tumor development and life span: Relation to glucocorticoid and tumor necrosis factor α levels in rats

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

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