Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model

Crit Care Med. 1994 Jun;22(6):914-21.


Objective: To test the hypothesis that induction of heat shock proteins before the onset of sepsis could prevent or reduce organ injury and death in a rat model of intra-abdominal sepsis and sepsis-induced acute lung injury produced by cecal ligation and perforation.

Design: Prospective, blind, randomized, controlled trial.

Setting: University research laboratory.

Subjects: One-hundred forty-two adult Sprague-Dawley rats (weight range 200 to 300 g).

Interventions: Production of intra-abdominal sepsis and exposure to heat stress. Animals were randomly divided into four groups: heated and septic, heated and sham-septic, unheated and septic, and unheated and sham-septic.

Measurements and main results: We evaluated the mortality rate and pathologic changes in lung, heart, and liver at 18 hrs after cecal perforation, at 24 hrs after removal of the cecum, and at 7 days after perforation. Heated animals exhibited a maximum increase in heat shock protein of 72 kilodalton molecular weight protein concentrations in the lungs and heart 6 to 24 hrs after the hyperthermic stress. By 18 hrs after perforation, 25% of the septic, unheated animals had died whereas none of the septic heated animals had died (p < .005). Septic, heated animals showed a marked decrease in 7-day mortality rate (21%) compared with septic unheated animals (69%) (p < .01). Furthermore, septic heated animals showed less histologic evidence of lung and liver damage than septic unheated animals.

Conclusions: These data suggest that thermal pretreatment, associated with the synthesis of heat shock proteins, reduces organ damage and enhances animal survival in experimental sepsis-induced acute lung injury. Although the mechanisms by which heat shock proteins exert a protective effect are not well understood, these data raise interesting questions regarding the importance of fever in the protection of the whole organism during bacterial infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Gene Expression Regulation
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / biosynthesis*
  • Heat-Shock Proteins / genetics
  • Hyperthermia, Induced
  • Liver / pathology
  • Lung / pathology
  • Molecular Weight
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / mortality
  • Multiple Organ Failure / pathology
  • Multiple Organ Failure / prevention & control
  • Prospective Studies
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / pathology
  • Respiratory Distress Syndrome / prevention & control*
  • Shock, Septic / complications
  • Shock, Septic / mortality
  • Shock, Septic / pathology
  • Shock, Septic / therapy*
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism*
  • Time Factors


  • Heat-Shock Proteins