Effects of splenectomy and GTS-21, a selective α7 nicotinic acetylcholine receptor agonist, on the development of septic ileus in mice

Sepsis remains a leading cause of mortality in our ICUs. Ileus, defined as the inhibition of the propulsive motility in the gastrointestinal (GI) tract, together with mucosal barrier dysfunction will maintain sepsis by the translocation of intestinal bacteria. Preliminary data in our group showed that the administration of GTS-21, a selective alpha7 nicotinic acetylcholine receptor (α7nAChR) agonist, ameliorates inflammation and GI motility disturbances during sepsis [1]. Activation of the α7nAChR is the final step in the vagal anti-inflammatory pathway, a spleen-dependent and macrophage-dependent pathway that dampens inflammation. We aimed to study the effects of splenectomy (SPLX) combined with GTS-21 on GI motility and on local colonic and systemic inflammation, as the role of the spleen in the vagal anti-inflammatory pathway is currently under debate.