1,25(OH)₂D₃ prolongs islet graft survival by inflammatory inhibition

Objective This study aimed to determine the protective effect of 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) against islet graft loss. Methods Proliferation of tumor necrosis factor (TNF)-α-induced macrophages was determined in vitro after treatment with different concentrations of 1,25-(OH)₂D₃. Intraportal islet transplantation (IPIT) was performed with islets harvested from the Sprague-Dawley rats and transplanted to the diabetic rats. The transplanted rats were assigned to receive 1,25-(OH)₂D₃ or propylene glycol (control). Islet graft survival; inflammatory cytokine (TNF-α and interleukin [IL]-1); numbers and percentages of macrophages, CD4⁺, and CD8⁺ T cells in bloods; and expression of nuclear factor (NF)-κB and TNF-α were analyzed. Hematoxylin and eosin staining was performed. Results We found 100 mg/mL 1,25-(OH)₂D₃ per day to have the strongest inhibitory effect on macrophages. Survival time of islet grafts significantly increased in the rats receiving 1,25-(OH)₂D ₃. There were fewer infiltrated inflammatory cells in both islet graft and adjacent tissue in the drug-treated rats with lower serum IL-1 and TNF-α. Furthermore, percentage of macrophages and expression of p-NF-κB p65 and TNF-α in graft sites were significantly lower in the treated rats. Conclusion Our results demonstrated that 1,25(OH) ₂D₃ prolongs islet graft survival by decreasing nonspecific inflammation in syngeneic IPIT through inhibiting TNF-α/NF-κB pathway and macrophage infiltration.