The NF-κB–mediated transcription of proinflammatory genes, in turn, is amplified within and across cells by induction of TLRs and cytokine receptors (e.g., those that belong to the IL-1β receptor family), which induce innate immune gene expression. Amplification of innate immune gene induction across cells and tissues can cause pathology, such as sepsis. Sepsis and systemic inflammatory-response syndrome involve a “cytokine storm.” This potentially fatal innate immune reaction consists of positive feedback loops between cytokines and immune and tissue cells, resulting in highly elevated levels of cytokines in the blood, multiorgan failure, and death (Osterholm 2005). Models of sepsis that involve activation of an acute phase-like response lead to increases in the levels of multiple cytokines in the blood that occur in two distinct phases. First, both TNF-α and IL-1β levels increase during the first several hours after infection but then subside. Subsequently, levels of HMGB1, a ubiquitously expressed, cytokine-like protein that can activate TLR4 and potentiate cytokine responses, increase about 16 hours after infection and remain elevated for several days (Wang et al. 2001). In mouse models, sepsis-induced death that
