Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release
large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate
tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown …

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-
activated macrophages, has been implicated as an important mediator of the lethal effect of
endotoxin. Recombinant human cachectin was infused into rats in an effort to determine …

Vertebrates achieve internal homeostasis during infection or injury by balancing the
activities of proinflammatory and anti-inflammatory pathways. Endotoxin
(lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to …

Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a
potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ
failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide …

Inflammation is a local, protective response to microbial invasion or injury. It must be fine-
tuned and regulated precisely, because deficiencies or excesses of the inflammatory
response cause morbidity and shorten lifespan. The discovery that cholinergic neurons …

Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and
mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis
and inflammatory bowel disease 1, 2, 3, 4. Highly conserved, endogenous mechanisms …

High-mobility group box 1 protein (HMGB1), which previously was thought to function only
as a nuclear factor that enhances transcription, was recently discovered to be a crucial
cytokine that mediates the response to infection, injury and inflammation. These …

Lipopolysaccharide (LPS) is lethal to animals because it activates cytokine release, causing
septic shock and tissue injury. Early proinflammatory cytokines (eg, tumor necrosis factor
[TNF] and interleukin [IL]-1) released within the first few hours of endotoxemia stimulate …

Nitric oxide (an endothelium-derived relaxing factor) induces smooth muscle relaxation and
is an important mediator in the regulation of vascular tone. Advanced glycosylation end
products, the glucose-derived moieties that form noncnzymatically and accumulate on long …

Cytokine production by the immune system contributes importantly to both health and
disease. The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit
cytokine release and thereby prevent tissue injury and death. The efferent neural signaling …