Figure 1. The activation of nuclear factor (NF)-B, an intracellular protein that regulates the transcription of many cytokine genes, is a multistep process that involves numerous upstream molecules. As shown in this simplified diagram, bacterial molecules such as lipopolysaccharide (LPS) are thought to interact, via CD14, with one or more Toll-like receptors (TLRs) in the plasma membrane. LPS-binding protein (LBP) facilitates this interaction. The kinase pathway from TLR to NF-B seems to be very similar to that used by the interleukin-1 receptor (IL-1R); this pathway converges with the tumour necrosis factor receptor (TNFR) pathway at the kinase called NF-B-inducing kinase (NIK). IB, inhibitory B; IKK, IB kinase; IRAK, interleukin-1 receptor-associated kinase; MyD, myeloid differentiation; TRADD, TNFR-associated death domain; TRAF, TNFR-associated factor.

Figure 2. Overview of inflammation-associated clotting. Intravascular fibrin formation is promoted when activated monocytes and endothelial cells express tissue factor, the key factor for initiating coagulation, and by decreases in the circulating levels of natural anticoagulant proteins (C and S antithrombin III). Fibrin removal is decreased by high blood levels of plasminogen activator inhibitor-1 (PAI-1). Fibrin, platelets and leucocytes accumulate in microvascular thrombi, which are thought to play an important role in multiorgan failure.