Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice.

摘要: Potentially fatal physiologic and metabolic derangements can occur in response to bacterial infection animals man. Recently it has been shown that alterations the levels of circulating cytokines such as IL-6 TNF-alpha shortly after challenge. To understand better role inflammation, we investigated effects vivo anti-mouse antibody treatment a mouse model septic shock. Rat neutralizing mAb was produced from splenocytes an animal immunized with rIL-6. This mAb, MP5-20F3, very potent specific antagonist vitro bioactivity, demonstrated using NFS60 myelomonocytic KD83 plasmacytoma target cell lines, also immunoprecipitated radiolabeled IL-6. Anti-IL-6 pretreatment mice subsequently challenged lethal doses i.p. Escherichia coli or i.v. protected death caused by these treatments. Pretreatment E. coli-challenged anti-IL-6 led increase serum TNF comparison isotype control antibody, implicating negative modulator vivo. Anti-TNF-alpha live resulted 70% decrease levels, determined immunoenzymetric assay, compared thereby supporting for positive regulator levels. We conclude is mediator infection, suggest antagonists may be beneficial therapeutically life-threatening infection.