Inhibitory effects of amitriptyline on granuloma formation in a chick-based experimental model

Granulomatous inflammation, a hallmark of chronic diseases, demands safer therapies due to the limitations of cur- rent immunosuppressive regimens. This study explores the repurposing potential of amitriptyline, a tricyclic antidepres- sant, for modulating granuloma formation and systemic immune responses in a chick-based experimental model. Subcu- taneous cotton pellet implantation was used to induce granulomas in chicks (n=6/group), followed by oral administration of amitriptyline (50 or 100 mg/kg/day) or a vehicle for 7 days. Granuloma wet and dry masses were calculated, and hematological profiling of white blood cells (WBCs) was performed. Amitriptyline significantly suppressed granuloma development in a dose-dependent manner, with 100 mg/kg reducing wet and dry masses by 17.73% (135.91±1.05 mg vs. control 165.20±1.42 mg) and 30.94% (49.10±1.02 mg vs. control 71.08±1.15 mg), respectively (P<0.05). Concur- rently, the WBC counts decreased by 23.2% (18116±97 vs. control 23583±410 cells/µl), with pronounced reductions in heterophils, lymphocytes, eosinophils, and basophils (P<0.05). These findings highlight amitriptyline’s dual anti-inflam- matory action, attenuating both granulomatous tissue formation and systemic leukocyte mobilization. While the chick model offers ethical and practical advantages, translational validation in mammalian systems is warranted. This study positions amitriptyline as a promising candidate for repurposing in granulomatous disorders, advocating for mechanistic investigations and clinical trials to harness its immunomodulatory potential.