title: Altered inflammatory gene expression underlies increased susceptibility to murine postoperative ileus with advancing age.
abstract: Susceptibility to postoperative ileus following abdominal surgery increases with advancing age. The mechanisms underlying this phenomenon are unknown. This study compares functional and molecular endpoints between young-adult (2 mo old), middle-aged (15 mo old), and elderly mice (26-30 mo old) to identify potential mechanisms. Susceptibility to ileus was assessed by measuring gastrointestinal transit (geometric center) 24 h after anesthesia, laparotomy, and light manipulation (LM) of the small bowel. Proinflammatory (IL-6, COX-2, inducible nitric oxide synthase) and anti-inflammatory (IL-10, heme oxygenase-1) gene and protein expressions were determined by real time RT-PCR, Western blot, and ELISA. LM did not alter gastrointestinal transit in young animals (geometric center = 8.8 +/- 0.9), but transit was increasingly delayed in middle-aged (6.9 +/- 0.8, P = 0.03) and elderly animals (4.7 +/- 0.6, P = 0.013). Despite the lack of LM effect on transit in young mice, IL-6 and COX-2 mRNA expressions were significantly increased postoperatively (165 +/- 24-fold and 2.9 +/- 0.3-fold, respectively). Expressions were increased further in middle-aged mice (1,103 +/- 187-fold; 4.4 +/- 0.7-fold) and further still in elderly mice (1,218 +/- 168-fold; 6.9 +/- 0.3-fold). IL-10 and heme oxygenase-1 gene expressions were also elevated postoperatively in young mice (4.8 +/- 0.5-fold and 13.0 +/- 1.3-fold, respectively) and were further increased in middle-aged mice (7.5 +/- 0.6-fold; 21.8 +/- 3.2-fold). However, inductions in elderly mice were significantly blunted (5.8 +/- 0.9-fold; 16.9 +/- 0.8-fold). There is both an age-dependent increase in the proinflammatory mediator expression and an age-dependent decrease in anti-inflammatory mediator expressions following minor insult to the bowel. Such imbalances between pro- and anti-inflammatory mechanisms may form the basis for increased susceptibility to ileus and for the increased severity and duration of ileus observed in the elderly.
authors.affiliation: Dept. of Medicine/Gastroenterology, Univ. of Pittsburgh Medical School, S849 Scaife Hall, 3550 Terrace St., Pittsburgh, PA 15261, USA. tbauer@pitt.edu
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Moore
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Albers
authors.forename: Brian M
authors.initials: BM
authors.lastname: Davis
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
authors.forename: Sandra
authors.initials: S
authors.lastname: Tögel
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D013505:Digestive System Surgical Procedures / Q000009:adverse effects*; D004195:Disease Models, Animal; D005772:Gastrointestinal Transit / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D045823:Ileus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053612:Janus Kinases / Q000378:metabolism; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011312:Pressure / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D050791:STAT Transcription Factors / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D016753:Interleukin-10; D051547:Heme Oxygenase-1; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053612:Janus Kinases