Mechanisms of Increased Survival in Lipopolysaccharide-Treated Mice With a Single Subcutaneous Capsaicin Challenge

Background: Capsaicin, a pungent compound present in capsicum fruits, has various biological activities such as stimulation of transient receptor potential vanilloid-1 (TRPV-1) and/or inhibition of tumor necrosis factor-alpha (TNF-α). This study aimed to reveal the mechanism involved in capsaicin-mediated high survival rate in LPS-treated mice. Methods: In LPS-treated mice, a comparative survival rate study using a TRPV-1 agonist (capsaicin) and a TRPV-1 antagonist (capsazepine). DNA-binding activity of NF-ĸB and TUNEL staining was conducted in vivo. In LPS-treated RAW264 cells, TNF-α was measured by enzyme-linked immunosorbent assay. Results: In the present study, the survival rate of mice treated with 20 mg/kg LPS was significantly improved from 7.7% to 92.3% after treatment with 4 mg/kg capsaicin and to 53.8% with 40 mg/kg capsazepine. In liver tissues, the LPS-induced increase in NF-ĸB DNA-binding activity was attenuated by capsaicin. The increased number of TUNEL-positive cells observed in the alveolar epithelial and liver parenchymal cells of LPS-treated mice was diminished by capsaicin treatment. In RAW264 cells, mouse leukemic monocytes, capsaicin inhibited the release of TNF-α after LPS stimulation, by attenuating NF-κB DNA-binding activity. Conclusion: The improvement in the survival rate (92.3% -high) by capsaicin administration in LPS challenge could be explained not only by TRPV-1 activity, but also by the pleiotropic effect which inhibits TNF-α release from macrophages. Thus, capsaicin may be a promising treatment option for LPS-related diseases such as severe sepsis or septic shock.