Harnessing the Power of Chlorogenic Acid: Inhibiting IL-2-Mediated Treg Upregulation to Combat Post-Traumatic Osteomyelitis.

Abstract

BACKGROUND: Chlorogenic acid (CGA) exerts immunomodulatory effects by regulating the proportion of regulatory T cells (Tregs), and T-cell dysregulation is a known feature of post-traumatic osteomyelitis (PTO). This study explored the mechanism of CGA in the treatment of PTO from the perspective of T-cell immunity. METHODS: Lymphocytes isolated from rat spleens were stimulated with interleukin (IL)-2. A PTO model was established by injectinginto the tibial marrow cavity of New Zealand white rabbits. PTO rabbits were treated with either CGA by gavage or lentiviral IL-2 injection. The Treg proportion was evaluated by flow cytometry. The expression of forkhead box protein 3 (), cytotoxic T lymphocyte antigen-4 (), and IL-2 was quantified by quantitative real-time polymerase chain reaction. The concentrations of tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), IL-10, and IL-2 were measured using enzyme-linked immunosorbent assays. Micro-computed tomography and hematoxylin and eosin staining were performed to characterize bone destruction. The proliferation of CD4T/CD8T cells was evaluated by flow cytometry. RESULTS: IL-2 stimulation elevated the proportion of Tregs in rat splenic lymphocytes, upregulated,, and IL-10 expression, and decreased TNF-&#x3b1; expression (< 0.05). PTO rabbits exhibited significant bone destruction and inflammatory cell infiltration in bone tissue. In the peripheral blood of PTO rabbits, the Treg proportion was elevated, with increased expressions of,, IL-10, and IL-2, reduced TNF-&#x3b1; expression, and increased proliferation of CD4T/CD8T cells. These changes were significantly reversed by CGA administration (< 0.001). However, the reversal effects of CGA were offset by exogenous IL-2 (< 0.001). CONCLUSION: CGA alleviates PTO by inhibiting IL-2-mediated upregulation of Tregs.