Role of tumor necrosis factor-α in lipopolysaccharide-induced pathologic alterations

摘要: Tumor necrosis factor-alpha (TNF) has been implicated strongly as a principal mediator in the pathogenesis of septic shock. The authors investigated vivo production TNF CBA/J and CD-1 mice that had primed by an intraperitoneal injection complete Freund's adjuvant followed 2 weeks later lipopolysaccharide (LPS). bioactivity peaked both ascites plasma one hour after challenge, mRNA expression cells 30 minutes LPS. After induction bioactivity, interstitial pulmonary neutrophilic infiltrate occurred was quantitated morphometrically myeloperoxidase (MPO) assay. Peripheral blood neutrophilia lymphopenia developed LPS (PMNs: control, 46 +/- 2%; LPS, 65 3%; Lymphs 53 37 3%). Treatment with dexamethasone (Dex) completely inhibited measured Because Dex will inhibit several cytokines, anti-TNF antiserum given to at same time challenge assess specifically role inducing these changes. This partially blocked neutrophil infiltrate, peripheral changes These data demonstrate plays important early pathophysiologic alterations occur systemic exposure