Significance of endogenous glucocorticoid sensitivity for airway eosinophilia in a murine model of allergy.

CONCLUSIONS

Endogenous GC protects against allergic inflammatory responses in the airways. These effects are modulated by both peripheral blockade and inhibition of release. Individual response patterns to stress, i.e. corticosterone release and peripheral sensitivity, may influence both the central and peripheral levels of the allergic airway reaction in patients.

OBJECTIVE

Glucocorticoids (GCs) modulate the allergic inflammatory response. Acute or chronic stress will influence circulating levels of GCs, rates of secretion, metabolism and target tissue sensitivity. In a clinical situation, stress may exacerbate or attenuate the asthmatic reaction. The aim of this study was to investigate the effects of inhibition of endogenous GC in an allergic airway inflammation model in the mouse.

MATERIAL AND

METHODS

An ovalbumin model using i.p. sensitization and intra-nasal challenge was used for respiratory eosinophilic inflammation. GC release was inhibited by administration of metyrapone (ME), and peripheral glucocorticoid receptors were blocked by administration of RU486 (RU).

RESULTS

Inhibition with RU and ME increased eosinophilia in the bone marrow compared to controls (p < 0.05). Eosinophilia in bronchoalveolar lavage fluid increased in the sensitized groups compared to controls, but there were no differences between the sensitized groups. CD3+ and CD4+ cells were increased in the nasal mucosa as a result of treatment with RU and ME.