Mechanisms of Glucocorticoid Resistance in Hypereosinophlic Syndromes

Glucocorticoids (GC) are anti-inflammatory agents commonly used to treat patients with hypereosinophilic syndrome (HES). GC promote eosinophil apoptosis and downregulation of Th2 cytokine production. Although abnormalities of GC receptor (GR) function and elevations in β-GR isoforms have been implicated in GC resistance in asthma, little is known about the mechanisms of GC resistance in HES. To explore the etiology of GC-resistance in HES, samples were analyzed from 19 subjects with HES enrolled on a prospective study of GC-responsiveness and 33 subjects with HES enrolled on a natural history study of eosinophilia for whom response to GC was known. GC responders were defined by a reduction in absolute eosinophil count (AEC) to in vitro (n=7). These data suggest that increased IL-5 may play a major role in GC resistance in HES.