Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation.

CNI-1493 is a potent anti-inflammatory agent, which deactivates macrophages and inhibits the synthesis of proinflammatory mediators. The objective of the present study was to identify the role of the central nervous system (CNS) and efferent vagus nerve signaling in CNI-1493-mediated modulation of acute inflammation in the periphery. CNI-1493 was administered either intracerebroventricularly (i.

Stimulus-dependent effects in the actions of sodium channel blockers on sensory C-units.

Stimulus-dependent inhibition of discharges from cutaneous C fibers from mechanothermo-sensitive (MTS) units (nociceptive sensors) can explain the paradoxical analgesic effect of local anesthetics at low concentrations, insufficient to block axonal conduction of nerve impulses. Three types of experiments are proposed which could detect the stimulus-dependent inhibition of the terminal section of sensory C units: a method involving repeated series of stimuli, the increasing stimulus method, and the spike encounter method. The applications of these methods to assessing the magnitudes of the neuroleptic effects of local anesthetics and cardiac antiarrhythmics is discussed.

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin.

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 release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms.

Spermine inhibition of monocyte activation and inflammation.

The innate immune system functions as a defensive front line against pathogenic invasion, but the proinflammatory products of activated monocytes and macrophages (e.g., TNF and NO) can also injure normal cells.

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.