Acute Inflammation and Microthrombosis Induced by Endotoxin, Interleukin-1, and Tumor Necrosis Factor and their Implication in Gram-Negative Infection

Abstract

Acute inflammation constitutes the body’s principal mode of defense against infection and other harmful agents, and neutrophils are the primary effector cells in this process. When inflammation occurs in response to infection with pathogenic microorganisms, the damage that is often observed locally is a sacrifice aimed to prevent the spread of infectious agents throughout the body. Gram-negative microorganisms elicit a brisk inflammatory reaction which is largely induced by one of their cell wall constituents, endotoxin. The infiltrating neutrophils phagocytose and kill the bacteria. The inflammatory reaction is often associated with severe local microvascular injury and abscess formation. Besides eliciting inflammation, endotoxin can predispose the local microvasculature to thrombosis upon subsequent systemic endotoxemia or complement activation, as demonstrated by the local Shwartzman reaction. Both the inflammatory and the thrombotic phenomena induced by endotoxin are mediated by the local generation of cytokines.