Mechanisms of polymicrobial sepsis-induced ileus.
Sepsis frequently occurs after hemorrhage, trauma, burn, or abdominal surgery and is a leading cause of morbidity and mortality in severely ill patients. We performed experiments to delineate intestinal molecular and functional motility consequences of polymicrobial sepsis in the clinically relevant cecal ligation and puncture (CLP) sepsis model. CLP was performed on male Sprague-Dawley rats. Gastrointestinal transit, colonic in vivo pressure recordings, and in vitro muscle contractions were recorded. Histochemistry was performed for macrophages, monocytes, and neutrophils. Inflammatory gene expressions were quantified by real-time RT-PCR. CLP delayed gastrointestinal transit, decreased colonic pressures, and suppressed in vivo circular muscle contractility of the jejunum and colon over a 4-day period. A leukocytic infiltrate of monocytes and neutrophils developed over 24 h. Real-time RT-PCR demonstrated a significant temporal elevation in IL-6, IL-1beta, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, with higher expression levels of IL-6 and inducible nitric oxide synthase in colonic extracts compared with small intestine. Polymicrobial CLP sepsis induces a complex inflammatory response within the intestinal muscularis with the recruitment of leukocytes and elaboration of mediators that inhibit intestinal muscle function. Differences were elucidated between endotoxin and CLP models of sepsis, as well as a heterogeneous regional response of the gastrointestinal tract to CLP. Thus the intestine is not only a source of bacteremia but also an important target of bacterial products with major functional consequences to intestinal motility and the generation of cytokines, which participate in the development of multiple organ failure.
Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Marcus
M
Overhaus
Sandra
S
Tögel
Michael A
MA
Pezzone
Anthony J
AJ
Bauer
D000818:Animals; D002432:Cecum / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D005769:Gastrointestinal Motility / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology; D045823:Ileus / Q000209:etiology* / Q000382:microbiology / Q000503:physiopathology; D007150:Immunohistochemistry; D007420:Intestine, Large / Q000382:microbiology / Q000503:physiopathology; D007421:Intestine, Small / Q000382:microbiology / Q000503:physiopathology; D007813:Laparotomy; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications* / Q000382:microbiology
D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat