title: Induction of the heat shock response prevents tissue injury during acute inflammation of the rat ileum.
abstract: OBJECTIVE
  To determine if prior total body hyperthermia protected against subsequent acute ileitis induced by the cytotoxic lectin, ricin, in rats. The time course of heat shock mRNA and protein expression in the ileum was determined. The effects of heat stress on small intestinal mucosal integrity, arachidonic acid metabolism, and neutrophilic infiltrate were compared in heated and nonheated rats receiving vehicle or ricin intraluminally. The effect of hyperthermia on the circulating neutrophil superoxide production was also evaluated.
  
  
  METHODS
  Prospective, randomized, controlled trial.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Forty-one adult, male Sprague-Dawley rats, weighing 150 to 250 g, and 32 adult, inbred, male Fisher 344 rats, weighing 175 to 250 g.
  
  
  METHODS
  Exposure to whole body hyperthermia and production of acute ileitis. Sprague-Dawley rats were divided randomly into four experimental groups: nonheated control group, heated control group, nonheated ricin group (1 mg/mL water, intraluminal), and heated ricin group. Sprague-Dawley rats in a separate study were assigned to seven groups based on the time of removal of the terminal ileum following hyperthermia: 0 min, or 1, 2, 4, 8, 12, and 24 hrs. Inbred Fisher 344 rats were allocated to the heated and nonheated groups for peripheral neutrophil superoxide generation studies.
  
  
  RESULTS
  Whole body hyperthermia to a rectal temperature of 41 degrees C to 42 degrees C for 15 to 20 mins: a) was associated with marked mucosal cytoprotection against subsequent ricin-induced ileitis (Injury grade [from 0 = normal to 5 = severe]: 0.4 +/- 0.1 vs. 2.5 +/- 0.2, p < .001); b) prevented the ricin-induced reduction in villus height to crypt depth ratio (2.4 +/- 0.1 vs. 1.9 +/- 0.1, p < .01); and c) significantly reduced the number of infiltrating neutrophils when compared with nonheated ricin-treated rats (11 +/- 2 vs. 32 +/- 3 neutrophils/high-power field, p < .001). The hyperthermia-induced peak increase in heat shock protein (HSP)-70 mRNA at 2 hrs preceded that of HSP 70i at 4 hrs. Heat shock significantly reduced the ricin-induced increase in both basal (8.0 +/- 1.9 vs. 33.0 +/- 8.1 pg of leukotriene B4/mg protein, p < .05) and ionophore-stimulated (16.0 +/- 4.9 vs. 80.0 +/- 15.5 pg of leukotriene B4/mg protein, p < .001) generation of ileal leukotriene B4, but did not alter the cyclooxygenase product, prostaglandin E2. Hyperthermia did not alter peripheral neutrophil superoxide production.
  
  
  CONCLUSIONS
  This study assessed the effects of heat shock in the normal and acutely inflamed intestine. These data suggest that heat stress and increased expression of HSP 70i protect against acute intestinal inflammation. This protection is associated with significant reductions in ileal leukotriene B4 generation and neutrophilic infiltrate. Hyperthermia did not alter circulating neutrophil superoxide production. Thus, the mechanism of heat stress protection against acute ileitis may involve local intestinal inhibition of leukotriene B4 production and subsequent neutrophilic infiltration without altering the ability of systemic neutrophils to be activated.
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
authors.forename: A
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: J
authors.initials: J
authors.lastname: Kiang
authors.forename: J
authors.initials: J
authors.lastname: Goldhill
authors.forename: D
authors.initials: D
authors.lastname: Matin
authors.forename: R
authors.initials: R
authors.lastname: Smallridge
authors.forename: R
authors.initials: R
authors.lastname: Galloway
authors.forename: T
authors.initials: T
authors.lastname: Shea-Donohue
mesh_terms: D000818:Animals; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D007079:Ileitis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D007082:Ileum / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012276:Ricin / Q000633:toxicity*
chemical_list: D006360:Heat-Shock Proteins; D012276:Ricin