Anti-inflammatory activity of caffeine (1,3,7-trimethylxanthine) after experimental challenge with virulent Listeria monocytogenes in Swiss mice

[Display omitted] •Caffeine did not exert direct antibacterial activity against L. monocytogenes.•Treatments with caffeine increase cell viability of infected macrophages.•Caffeine treatments reduced leukocyte recruitment after infection in mice.•Caffeine treatments diminished the bacterial burden in spleen and the liver.•The mRNA expressions of IL-1β, IL-6 and iNOs were reduced after infection. Immunomodulatory therapies are claimed to enhance antimicrobial immunity and counterbalance antimicrobial resistance mechanisms of pathogenic bacteria. To investigate whether caffeine can be useful for control of inflammation derived from experimental systemic infection with Listeria monocytogenes. Peritoneal macrophages (pMØ) from Swiss mice were cultured with caffeine in 96-well plates, and then infected with virulent L. monocytogenes 619. In another experiment, the pMØ were first infected with the bacterium and then treated with caffeine. Swiss mice were inoculated intraperitoneally with L. monocytogenes and then treated intravenously with caffeine (0.05; 0.5 or 5 mg/Kg). Caffeine did not exert direct antibacterial activity in vitro against L. monocytogenes. Macrophages exposed to caffeine before or after infection with L. monocytogenes had increased cell viability, although the intracellular bacterial loads were similar to the control groups. Caffeine treatments of Swiss mice reduced leukocyte infiltration into the peritoneal cavity after L. monocytogenes infection. However, the bacterial burden was reduced in the spleen and liver. The mRNA expressions of IL-1β, IL-6 and the enzyme inducible nitric oxide synthase (iNOS) were reduced whereas IL-10 was increased. Caffeine has an anti-infectious potential and ameliorated infection-derived inflammation following experimental infection with L. monocytogenes.