Impaired gut contractility following hemorrhagic shock is accompanied by IL-6 and G-CSF production and neutrophil infiltration

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel sta sis. The aim of this study was to examine whether or not HS initiates an in flammatory response that includes production of cytokines, specifically G-C SF and interleukin-6 (IL-6), and recruitment of leukocytes within the intes tinal muscularis which contribute to impaired muscle contractility. Sprague -Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by re suscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous an d bethanechol-stimulated muscle contractility Semiquantitative RT-PCR demon strated elevated revels of IL-6 and G-CSF mRNA in shock animals in fun-thic kness jejunum and in mucosa and muscularis layers compared to sham controls . Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G -CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers o f shock animals. Activation of Stat3 also was demonstrated in normal muscul aris tissue exposed to IL-6 and G-CSF in vitro. IL-B and C-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contri bute to PMN recruitment and smooth muscle dysfunction.