Figure 1. Intrinsic (DAMPs) and extrinsic (PAMPs) signals develop during an infectious condition (e.g. bacterial pneumonia) that causes inflammation and sepsis which is often associated with development of SIRS, buildup of ROS and RNS in tissues, multiorgan failure (MOF) and lethality.

Receptors (PRRs) for these signals engage both TLRs and NOD-like receptors. The listings of ligands that interact with TLRs and NOD receptors is somewhat artificial. For instance, while HMGB1 (considered to be a DAMP) interacts with TLR4, it also interacts with TLR2 and with the receptor for advanced glycation products (RAGE). Heat shock proteins (DAMPs) react with TLR2, TLR4 and with receptors on antigen presenting cells (CD36, a scavenger receptors). ‘Sterile’ inflammation occurs after hemorrhagic shock, polytrauma, ischemia/reperfusion and is not usually associated with the presence of an infectious agent. In all cases, the same cascade of downstream events seems to occur.