Parental support and cytokine activity in childhood asthma: the role of glucocorticoid sensitivity

Abstract

Background: Stress is known to worsen the course of asthma, but the underlying mechanisms are poorly understood. This problem is especially difficult because stress elicits secretion of cortisol, a hormone that dampens airway inflammation and ameliorates asthma symptoms.

Objective: This article proposes that stress affects asthma by inducing resistance to the anti-inflammatory properties of glucocorticoids. To evaluate this hypothesis, we examine whether a particular kind of stress in children's lives, not feeling supported or understood by parents, is associated with in vitro measures of lymphocyte resistance to glucocorticoids and indices of eosinophil mobilization and activation.

Methods: Children with asthma (n = 67) and medically healthy children (n = 76) completed standardized questionnaires about support from their parents. PBMCs were collected and incubated with a mitogen cocktail in the presence of physiologic concentrations of hydrocortisone. Production of IL-5, IL-13, and IFN-gamma was measured by means of ELISA. Circulating eosinophils were enumerated with a hematology analyzer, and the extent of their activation was indexed by means of ELISA for eosinophil cationic protein.

Results: To the extent that children with asthma perceived low support from their parents, children were more resistant to hydrocortisone's anti-inflammatory effects on IL-5 and IFN-gamma production and had higher circulating levels of eosinophil cationic protein. These associations were independent of socioeconomic conditions, cigarette exposure, disease severity, and medication use.

Conclusions: These patterns suggest the hypothesis that strained parent-child relations, and perhaps stress more generally, brings about adverse outcomes in asthma by diminishing cortisol's ability to regulate cytokine activity and subsequent airway inflammation.