Interleukin-1β selectively increases substance P release and augments the ascending phase of the peristaltic reflex

Exposure of muscle strips to interleukin (IL)-1beta stimulates substance P (SP) expression, suggesting a link between IL-1beta and the increase in SP expression during intestinal inflammation. The present study examined whether the SP expression induced by IL-1beta is reflected by enhanced SP release and SP-mediated reflex activity. Exposure of innervated longitudinal colonic muscle strips to IL-1beta for 8 h increased SP synthesis in, and greater SP release from excitatory motor neurones in response to KCl or electrical field stimulation (EFS), and enhanced longitudinal muscle contraction in response to EFS. IL-1 Ra and IL-1beta antibody blocked IL-1beta-induced increase in SP release and muscle contraction. Neither vasoactive intestinal peptide (VIP) nor somatostatin release was increased. The increase in SP release was reflected in enhanced circular muscle contraction in response to stretch. VIP-mediated descending relaxation of circular muscle was not affected. The selective increase in ascending contraction induced by exposure to IL-1beta was blocked by IL-1 Ra or IL-1beta antibody. We conclude that the selective increase in SP expression induced by IL-1beta in excitatory motor neurones is reflected by enhanced SP release and longitudinal muscle contraction in response to EFS, and enhanced SP release and circular muscle contraction during the ascending phase of the peristaltic reflex.