RECENT findings have redefined our understanding of glucocorticoid-mediated eosinopoiesis in asthma, revealing a duality that challenges long-held assumptions about corticosteroid therapy. While glucocorticoids (GCs) are renowned for their anti-inflammatory and immunosuppressive actions, new evidence suggests that they may simultaneously promote bone marrow eosinophil production, introducing complexity into their clinical use.
Mechanisms Behind Eosinopoiesis in Asthma
The regulation of eosinopoiesis in asthma involves intricate signalling between GCs, cytokines, and the bone marrow microenvironment. Under certain immunological conditions, GCs interact with eosinopoietic cytokines such as interleukin-5 (IL-5) and cysteinyl-leukotrienes to enhance eosinophil progenitor differentiation and survival. This process links systemic endocrine signals to local inflammatory pathways, blurring the line between suppression and stimulation in asthma pathophysiology.
The Paradox of Glucocorticoid-Induced Eosinopoiesis
Traditionally, GCs have served as the cornerstone of asthma management, effectively suppressing airway inflammation, reducing Th2 cytokines such as IL-5 and IL-13, and promoting eosinophil apoptosis within the lungs. This results in improved lung function and fewer exacerbations. However, studies now highlight that in certain contexts, GCs can paradoxically enhance eosinopoiesis, the generation of eosinophils in the bone marrow. This occurs through interactions with eosinopoietic cytokines, including IL-5 and cysteinyl-leukotrienes, as well as stromal cell-derived factors that stimulate eosinophil progenitors.
This paradoxical effect appears to be context-dependent, influenced by factors such as infection, allergen exposure, and systemic stress. While GCs suppress eosinophilic inflammation in peripheral tissues, they may concurrently prime the bone marrow to release eosinophils once treatment is withdrawn. This phenomenon could explain why some patients experience asthma relapse or steroid resistance after tapering corticosteroids, as the marrow-derived eosinophil pool becomes rapidly mobilised upon exposure to new inflammatory stimuli.
The implications for clinical practice are significant. If glucocorticoid-mediated eosinopoiesis in asthma contributes to relapse or treatment resistance, monitoring bone marrow activity could enhance personalised asthma therapy. Emerging biomarkers, such as circulating eosinophil progenitors and serum IL-5 levels, may offer predictive insights into disease control and relapse risk.
Ultimately, this research invites a paradigm shift: rather than focusing solely on airway inflammation, clinicians may need to consider both peripheral and central (bone marrow) eosinophil dynamics. By integrating this systemic perspective, future therapies could better balance glucocorticoids’ beneficial anti-inflammatory properties with their paradoxical capacity to sustain eosinophil production, paving the way for more durable asthma control.
Reference
Vieira BM. Glucocorticoid-mediated modulation of eosinopoiesis in asthma: a paradoxical duality. Allergies. 2025;5(4):35.
