The TLR4-TLR2 interaction suggests a highly coordinated, oxidant-mediated upregulation of TLR2 in response to LPS. When one considers the interactions of the innate immune system as microbes are first encountered, the value of such temporal organization is significant. For example, Gram-negative bacteria persist in tissues and, if they are not immediately killed through the activation of PMN, complement and other antimicrobial factors, they may spill out systemically and result in septic shock. Survival in the face of such infections depends on the innate immune system, which must be able to monitor and respond to pathogens over a prolonged period of time. Given the need for a prolonged response to bacterial infection, it has always seemed somewhat surprising that response to LPS is temporally finite. This endotoxin tolerance means that within hours after exposure to LPS, innate immune cells are incapable of responding again to a rechallenge (69) . But it is now clear that as LPS sensitivity wanes, the immune system has at its disposal the capability of marshaling responses via oxidative metabolites and their ability to upregulate other TLRs (70) . The subsequent means of responding to bacteria depend on the ability of the innate immune system to destroy microbes and enhance the release of alternative immune stimuli. The TLRs that are utilized are the ones that bind the constituents of degrading bacteria, such as lipopeptides, PGN, heat shock proteins and CpG DNA. It seems plausible that activated PMN may even alter the phenomenon of LPS tolerance, at least in a localized context, by setting into action a positive feedback loop at sites to which PMN are chemoattracted (71) . This would enhance inflammatory responses locally and help fight infection. However, in a setting of posttrauma SIRS or ALI, the primed PMN activation serves as an amplifier to cause enhanced PMN infiltration and organ injury.