Intraperitoneal Treatment of Cambinol, a Synthetic SIRT1 and SIRT2 Inhibitory Compound, Exacerbates 544 Burden in the Spleens of Institute of Cancer Research Mice.

Our preliminary data using bone marrow-derived macrophages (BMDMs) collected from ICR mice treated with anti-sirtuin (anti-SIRT) 1 antibody showed that uptake was significantly attenuated. We then further investigated the effect of an inhibitor of SIRT1/2, cambinol, in the progression of . The in vitro results using RAW264.7 cells revealed that cambinol treatment had no effect on adhesion, uptake, intracellular survival and nitric oxide (NO) production during infection, nor did it directly affect bacterial growth for up to 72 h. Finally, intraperitoneal treatment of 8-week-old female ICR mice infected with showed no differences in the total average weights of spleens and livers; however, the treated mice displayed higher colony-forming units (CFUs) from the spleens. Furthermore, the interleukin (IL)-10 serum level was observed to be lower in treated mice at 7 d post-infection, and none of the cytokines tested showed a change at 14 d post-infection. The overall findings showed that cambinol treatment had no effect on the proliferation of in RAW264.7 macrophages but exacerbated the splenic proliferation of the bacteria in mice and displayed reduced anti-inflammatory cytokine IL-10 at the first week of infection, suggesting that cambinol as an inhibitory of SIRT1/2 could be beneficial in the context of dissemination in animal hosts and that exploration of activating SIRTs could be an alternative treatment against infection.