State of the Art 1769 suppressed trauma patients (27). New evidence suggests that the central nervous system can directly, and rapidly, attenuate the TNF response to endotoxin through efferent vagus nerve signals to tissue-resident macrophages (28). This effect is mediated by acetylcholine, the principal neurotransmitter of the vagus nerve, which signals via nicotinic cholinergic receptors present on macrophages (28). Thus, the complex cytokine milieu in septic patients is characterized by the interaction between antiinflammatory responses and potentially injurious proinflammatory responses that are tightly regulated by neural and humoral pathways.