Pharmacodynamic profile of Hexadimethrine Bromide-induced eosinophilia - Roles of pro-eosinophilic mediators

Hexadimethrine Bromide (HxB) has been reported to trigger marked eosinophilia even under conditions that typically cause eosinopenia. We investigated how HxB modulates eosinopoiesis and eosinophil accumulation in mice. Swiss Webster, C57BL/6, and BALB/c mice received HxB (1 or 10 mg/kg, intraperitoneally). Eosinophils were quantified in bone marrow, blood, and spleen by cytology and flow cytometry; serum cytokines/chemokines were profiled; serum transfer and montelukast pre-treatment tested mechanisms. HxB increased circulating and tissue eosinophils in a dose-dependent manner, peaking at 10 mg/kg, without neutrophilia. Bone marrow eosinopoietic potential rose, with higher frequencies of eosinophil-committed progenitors and mature eosinophils; effects generalized across strains. Serum from HxB-treated donors transferred eosinophilia to naïve recipients. A Th2-skewed burst of mediators (IL-3, IL-4, IL-5, IL-9, IL-13, eotaxin, RANTES, MIP-1α/β, and TNF-α) peaked at 24 h and returned to baseline by day 3. Montelukast did not blunt responses, indicating CysLT-independence. A second HxB dose on day 3 sustained eosinophilia through day 6. HxB elicits a rapid, cytokine-mediated, CysLT-independent pro-eosinophilic state that can be maintained with dosing every three days. This robust model yields abundant, mature eosinophils, supports mechanistic studies, and may inform future translational investigations of pharmacologically induced eosinophilia.