Fetuin, a negative acute phase protein, attenuates TNF synthesis and the innate inflammatory response to carrageenan.

Activation of the innate immune system, even by relatively innocuous stimuli, stimulates the release of cytokines (e.g. TNF) that can injure or kill the host.

Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes.

Background: Cytokines mediate the metabolic and physiologic responses to injury and infection. Anterior pituitary cells express receptors for tumor necrosis factor (TNF) and interleukin 1 (IL-1), which can signal these cells to release corticotropin, growth hormone, and cytokines such as IL-1 and macrophage migration inhibitory factor. This interaction provides an important link between the immune system and the neuroendocrine system.

HMG-1 as a late mediator of endotoxin lethality in mice.

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 limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model.

Hypophysectomy, high tumor necrosis factor levels, and hemoglobinemia in lethal endotoxemic shock.

Experimental models of lethal endotoxemia in rodents are widely used to delineate pathogenic mechanisms of inflammation, sepsis, and septic shock. One long-standing but poorly understood observation is that removal of the pituitary gland (hypophysectomy) renders experimental animals 1,000-fold more sensitive to the lethal sequelae of lipopolysaccharide (LPS). Previous explanations for this phenomenon focused on hypophysectomy-induced deficiencies of corticosteroids, because glucocorticoids effectively suppress the synthesis of tumor necrosis factor (TNF), which is a primary mediator of LPS lethality.

Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia.

Two contrasting roles, one beneficial and the injurious, have been proposed for tumor necrosis factor (TNF) in the pathogenesis of cerebral ischemia. Reported here are results obtained in a standard model of permanent focal cortical ischemia in rats, in which the volume of cerebral infarction is measured after permanent occlusion of the middle cerebral artery. Administration of neutralizing anti-rat TNF antibodies (P114) into the brain cortex significantly reduced ischemic brain damage (85% reduced infarct volume as compared with preimmune-treated controls).