RATIONALE: Inhibition of innate immune responses by circulating endogenous corticosteroids is important for protection against inappropriate inflammatory reaction in the lung. Psychosocial stress may alter corticosteroid responsiveness of innate immune cells that could, in turn, contribute to the acute inflammatory airway response. METHODS: We developed models of social disruption stress and allergic sensitization with an Aspergillus fumigatus extract in Balb/c mice. Circulating corticosterone levels, inflammatory cell influx, cytokine release and airway function were assessed following allergen challenge. Corticosteroid responsiveness and glucocorticoid receptor (GR) protein expression were studied in LPS-stimulated splenic mononuclear cells and in the lung tissue. mRNA expression for GR was studied in the spleen and lung tissue of the mice. RESULTS: Concomitant with NF-954;B activation, social stress increased CCL17 and IgG1 in the airways and in LPS-stimulated splenocytes suggesting a Th2-type predisposition of the innate immune system. Accordingly, in spite of markedly increased serum corticosterone levels, in comparison with controls, social stress enhanced airway responses to allergen challenge in sensitized mice and increased Th2-type cytokine, chemokine, TNFα and IL-6 levels. The combination of stress and allergen exposure also reversed the corticosterone effects on LPS-stimulated survival, Th2 cytokine, IgG1, CCL17, TNFα and IL-6 release by splenocytes. This effect was associated with decreased GR mRNA expression and nuclear translocation in the lung tissue and spleen, respectively. CONCLUSIONS: We speculate that stress predisposes to Th2-type immune changes and amplifies the allergic airway response. This occurs due to a diminished expression and function of GR in innate immune cells.
Full conference title:
American Academy of Allergy Asthma & Immunology
- AAAAI 2009 (65th)