Induction of the heat shock response prevents tissue injury during acute inflammation of the rat ileum

OBJECTIVES 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. DESIGN Prospective, randomized, controlled trial. SETTING University research laboratory. SUBJECTS 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. INTERVENTIONS Exposure to whole body hyperthermia and production of acute ileitis. Sprague-Dawley rats were divided randomly into four experimental groupsnonheated 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 hyperthermia0 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. MEASUREMENTS AND MAIN RESULTS Whole body hyperthermia to a rectal temperature of 41 degrees C to 42 degrees C for 15 to 20 minsa) 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 produ