%0 Journal Article
%T Ketamine inhibits tumor necrosis factor secretion by RAW264.7 murine macrophages stimulated with antibiotic-exposed strains of community-associated, methicillin-resistant Staphylococcus aureus
%A Thomas Spentzas
%A Rebekah KH Shapley
%A Carlos Aguirre
%A Elizabeth Meals
%A Lauren Lazar
%A Mark S Rayburn
%A Brett S Walker
%A B Keith English
%J BMC Immunology
%D 2011
%I BioMed Central
%R 10.1186/1471-2172-12-11
%X RAW264.7 cells exposed to either LAC or MW2 in the presence of daptomycin secreted less TNF than in the presence of vancomycin. The addition of ketamine inhibited macrophage TNF secretion after stimulation with either of the CA-MRSA isolates (LAC, MW2) in the presence of either antibiotic. The NMDA inhibitors, MK-801 and APV, also suppressed macrophage TNF secretion after stimulation with either of the antibiotic-exposed CA-MRSA isolates, and the effect was not additive or synergistic with ketamine. The addition of NMDA substrate augmented TNF secretion in response to the CA-MRSA bacteria, and the addition of APV suppressed the effect of NMDA in a dose-dependent fashion.Ketamine inhibits TNF secretion by MRSA-stimulated RAW264.7 macrophages and the mechanism likely involves NMDA receptor antagonism. These findings may have therapeutic significance in MRSA sepsis.Infections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) present a major public health problem because of recent increases in the incidence of these infections [1,2]. In a 2007 report, the Centers for Disease Control concluded that Staphylococcus aureus is now the most important cause of serious and fatal infection in the United States [3]. The prototypical USA400 strain, MW2, (CDC nomenclature for this strain of MRSA) was first isolated in 1999 from a Midwest child with fatal CA-MRSA pneumonia [4]. In 2003, the prototypical USA300 CA-MRSA strain, LAC, was isolated from Los Angeles County patients with skin and soft tissue infections, severe pneumonia and sepsis. Recently, concerns about CA-MRSA infections were heightened after reports of severe invasive staphylococcal infections in some patients infected with the novel 2009 H1N1 influenza A virus [5,6].CA-MRSA isolates express many virulence factors [7,8], including several cytolysins: ¦Á-toxin, ¦Ã-toxin, Panton-Valentine leukocidin (PVL), phenol-soluble modulins (PSMs), ¦Ä-toxin and, unlike traditional hospita
%U http://www.biomedcentral.com/1471-2172/12/11