BACKGROUND: The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distal target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase reactants (APRs), that carries out specific protective functions. This study investigates the response of positively regulated (alpha 1-acid glycoprotein and alpha 1-antitrypsin) and negatively regulated (albumin) APR genes to severe thermal injury in three rat strains with differing abilities to survive thermal stress. METHODS: Age and weight matched male Buffalo, Sprague-Dawley, and Fischer 344, 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled rat alpha 1-glycoprotein, rat albumin, and mouse alpha 1-antitrypsin cDNAs. Relative amounts of alpha 1-glycoprotein, alpha 1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. RESULTS: All three strains elicit both a positive and negative acute phase (AP) response. Significant differences were observed in the degree and kinetics between strains. Those more sensitive to thermal injury exhibited a more intense positive AP response and possibly a delayed recovery. The AP response between these strains correlates with the variation in ability to survive severe trauma. CONCLUSIONS: The differences in the kinetics and intensity of induction of APR genes between Buffalo, Sprague-Dawley, and Fischer rat strains suggest that the least intense AP response and its timely recovery correlated with the ability to survive a severe thermal injury and that, conversely, the more intense and prolonged response correlated with sensitivity to severe thermal injury. We propose that this may be a basis for variation in survival to thermal injury.
BACKGROUND: The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distal target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase reactants (APRs), that carries out specific protective functions. This study investigates the response of positively regulated (alpha 1-acid glycoprotein and alpha 1-antitrypsin) and negatively regulated (albumin) APR genes to severe thermal injury in three rat strains with differing abilities to survive thermal stress. METHODS: Age and weight matched male Buffalo, Sprague-Dawley, and Fischer 344, 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled rat alpha 1-glycoprotein, rat albumin, and mouse alpha 1-antitrypsin cDNAs. Relative amounts of alpha 1-glycoprotein, alpha 1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. RESULTS: All three strains elicit both a positive and negative acute phase (AP) response. Significant differences were observed in the degree and kinetics between strains. Those more sensitive to thermal injury exhibited a more intense positive AP response and possibly a delayed recovery. The AP response between these strains correlates with the variation in ability to survive severe trauma. CONCLUSIONS: The differences in the kinetics and intensity of induction of APR genes between Buffalo, Sprague-Dawley, and Fischer rat strains suggest that the least intense AP response and its timely recovery correlated with the ability to survive a severe thermal injury and that, conversely, the more intense and prolonged response correlated with sensitivity to severe thermal injury. We propose that this may be a basis for variation in survival to thermal injury.