Cytokine
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Tumor necrosis factor (TNFα) is a proinflammatory cytokine and has been a target for intervention in human sepsis. However, inhibition of TNF-α with a high dose of a TNF-receptor fusion protein in patients with septic shock worsened patient survival. This study was designed to investigate whether blocking TNF-α enhances mortality in infected burn mice through the induction of IL-1β. ⋯ Our findings suggest that thermal injury induces lung NF-κB activation and neutrophil sequestration through TNFα signaling. However, blocking TNF-α enhances P. aeruginosa infection-induced lung damage in burn mice via induction of IL-1β. Using an IL-1 receptor antagonist combined with the neutralization of TNF-α could be a useful strategy for decreasing P. aeruginosa infection-induced mortality in burn patients.
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Painful neuropathy is a common, difficult to treat complication of both Types 1 and 2 diabetes (T1D and T2D). Reports have shown that activation of inflammatory cascades play an important role in the development and persistence of neuropathic pain states, but it is not well established in painful diabetic neuropathy (PDN). Previously, studies have shown increased inflammatory cytokines in the serum of the diabetic patients with painful neuropathy. This study focuses on the changes in the levels of inflammatory mediators such as TNFα, interleukins, chemokines and cell adhesion molecules with the development of pain in the DRG of the Zucker diabetic fatty (ZDF) rat, an established model for T2D. This study also demonstrates an alteration in the levels of voltage gated sodium channel 1.7 (NaV1.7) with the development of pain in DRG of the ZDF rats. ⋯ The rise in inflammatory markers in the DRG of Type 2 diabetic animals and increases in voltage gated sodium channel NaV1.7 in DRG with the onset of pain in PDN suggest that inflammation in the DRG may play an important role in the development of pain in this model.