PMC:17823 / 548-2862 JSONTXT

{"project":"Colil","denotations":[{"id":"T1","span":{"begin":1159,"end":1160},"obj":"9854038"},{"id":"T2","span":{"begin":1824,"end":1826},"obj":"2242071"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/"}],"text":"Introduction:\nSeptic arthritis is a severe disease, which is associated with high mortality and rapid destruction of affected joints. The most common bacterial agent in this condition is S aureus, which is the responsible pathogen in 37–56% of all cases of septic arthritis. Despite eradication of bacteria from the joint cavity, destruction of the joint often continues, resulting in severe sequelae.\nIn our mouse model of sepsis and septic arthritis we use an intravenous inoculum of a S aureus strain (LS-1) that produces toxic shock syndrome toxin (TSST)-1. This bacterial strain was originally isolated in a mouse with spontaneous staphylococcal arthritis. IL-12 is a heterodimeric cytokine that is composed of the constitutively expressed p35 gene product and the inducible p40 subunit. It is primarily produced by monocytes/macrophages and dendritic cells.\nIL-12 has a variety of effects on natural killer cells and T cells, including the ability to facilitate T-helper (Th1)-cell responses, and thereby IFN-γ production. IFN-γ has been shown to be arthritogenic in septic arthritis, but protective with regard to bacterial clearance and survival. IL-12 is protective in several experimental models of bacterial infections, as demonstrated by the fact that neutralization of this cytokine increases susceptibility and addition of recombinant IL-12 ameliorates the severity of the infection. However, IL-12 given at high doses induces a septic shock-like condition, and neutralization of IL-12 protects mice from lipopolysaccharide-induced shock. Thus, the role of IL-12 in cases of severe bacterial infection that culminate in septic shock is not established.\nIt has recently been shown that IL-12 deficiency exists in humans and that absence of IL-12 gives rise to recurrent infections with S aureus. The role of IL-12 in S aureus infection has not previously been assessed. Inoculation of IL-12 p40-deficient mice and their wild-type counterparts with a TSST-1-producing S aureus strain shows the critical importance of IL-12 for survival during S aureus sepsis, in that it mediates downregulation of staphylococcal growth.\nThe aim of the present study was to investigate the importance of IL-12 in S aureus arthritis, specifically its impact on survival, bacterial clearance and development of arthritis."}