The new study connects CCK to a recently identified antiinflammatory pathway that is controlled by the vagus nerve. This pathway—dubbed the cholinergic antiinflammatory pathway—is mediated by the neurotransmitter acetylcholine, which is released from vagus nerve endings upon stimulation. Acetylcholine binds to nicotinic receptors on macrophages, thus inhibiting the synthesis and release of inflammatory cytokines such as TNF and interleukin (IL)-6.
Luyer et al. now show that the antiinflammatory effect of fat consumption in the rat model of hemorrhagic shock requires both CCK and the vagus nerve, as blocking CCK or severing the vagus nerve abolished this effect. With the vagus nerve intact, fat-induced CCK inhibited the production of circulating TNF and IL-6 and reduced gut permeability. Blocking nicotinic receptors also eliminated the antiinflammatory effects of dietary fat, thus solidifying the connection between fat-induced CCK and the cholinergic antiinflammatory pathway.
The authors think that this pathway might be important in suppressing gut inflammation in response to food proteins and normal gut bacteria, which immune cells might otherwise regard as foreign invaders. They also suggest that this pathway could potentially be targeted in patients as a way to reduce inflammatory complications after surgery.