title: Dextromethorphan efficiently increases bactericidal activity, attenuates inflammatory responses, and prevents group a streptococcal sepsis.
abstract: Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study.
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University Medical College, 1 University Road, Tainan 701, Taiwan.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Li
authors.forename: Yueh-Hsia
authors.initials: YH
authors.lastname: Luo
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Chang
authors.forename: Shiou-Ling
authors.initials: SL
authors.lastname: Lu
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Kuo
authors.forename: Jau-Shyong
authors.initials: JS
authors.lastname: Hong
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000517:prevention & control; D002470:Cell Survival / Q000187:drug effects; D003915:Dextromethorphan / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000382:microbiology* / Q000517:prevention & control*; D013290:Streptococcal Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D003915:Dextromethorphan