Hemostatic containment - an evolutionary hypothesis of injury by innate immune cells

Tissue damage mediated by innate immune cells in reperfusion injury may have a survival benefit in infections, preventing sepsis. Tissue damage by leukocytes - plugging of small vessels, endothelial cell damage, tissue edema around vessels, and stimulation of platelet aggregation - occurs in both reperfusion injury and infection-prone wounds. These events create a physical barrier that may sequester bacteria, preventing bacterial invasion of the blood. This antisepsis effect, termed "hemostatic containment," is triggered by signals that convey susceptibility to infection, such as poor blood flow and oxygenation. In active and incipient infections, the host accepts some sacrifice of body tissues while preventing pathogens from gaining access into sterile sites. This tradeoff prevents bacteremia and promotes survival in diseases such as abscesses. Other diseases mimic infection-prone states and elicit costly host injury that exceeds antibacterial benefits. Mimic diseases include cocaine-induced heart attacks and decompression illness. Mimics produce signals that active innate immune cells despite the absence of pathogens. Atherosclerotic cardiovascular diseases comprise an intermediate, or pseudo-mimic, state characterized by indolent pathogens that rarely cause sepsis. Treatment of innate immune cell injury is likely to be more effective for mimic and pseudo-mimic states than for infectious diseases. Interventions against reperfusion injury might be most effective when they improve host immune defenses while eliminating signals of infection risk.