Figure 6.

An immune challenge such as lipopolysaccharide (LPS) is detected by cells of the innate immune system, which respond by releasing pro-inflammatory cytokines such as TNFα. In response to systemic LPS, the spleen is known to be the major source of TNFα, which in turn plays a pivotal role in driving the full inflammatory response. At the same time, the immune challenge is detected by the CNS. As in the case of fever, this afferent signal is mediated by humoral factors such as inflammatory cytokines and/or prostaglandins. The CNS then responds by activating a specific subset of sympathetic nerves, whose function is to suppress excessive production of TNFα by the spleen. Other possible targets include the liver, cells in the gastrointestinal (G.I.) tract and the adrenal glands. Those anti-inflammatory nerve fibres run in the greater splanchnic nerve, which constitutes the efferent arm of the inflammatory reflex. Nerve pathways in the vagus do not contribute.