ABSTRACT
OBJECTIVE: Local cytokine production is a pathogenic factor in ischemia-reperfusion injury in early graft dysfunction. This study analyzed interleukin 8 (IL-8) messenger RNA (mRNA) expression in lung tissue and the association between IL-8 mRNA levels and interstitial lung changes in an experimental model of warm lung ischemia-reperfusion. MATERIAL AND METHODS: We studied 16 New Zealand rabbits divided into 3 groups: control, ischemia (tissue taken from right lower lobe after 1, 2, or 3 hours of ischemia), and reperfusion (tissue taken from right upper and middle lobes after 1 hour of ischemia and 1, 2, or 3 hours of reperfusion). Expression of IL-8 mRNA was determined by reverse transcription and polymerase chain reaction. Interstitial infiltration by polymorphonuclear neutrophils was determined. The Mann-Whitney U-test was used for statistical comparisons, with P< .05 considered to indicate a significant result. RESULTS: During ischemia, IL-8 mRNA levels were elevated at the end of hour 1 (P=.009) with respect to the control group, but not thereafter. Interstitial changes were minimal. IL-8 mRNA levels during reperfusion were similar to those observed during ischemia, with a slight increase at the end of hour 2. There were no significant differences between hours 1, 2, and 3. Polymorphonuclear neutrophil recruitment occurred at the beginning of reperfusion (P=.014), but no significant differences were observed at hours 2 or 3. Progressive thickening of alveolar septa and edema was documented. CONCLUSIONS: Changes in IL-8 mRNA expression during ischemia precede interstitial infiltration by polymorphonuclear neutrophils during reperfusion, suggesting that the 2 processes are related. Quantification of IL-8 mRNA expression could facilitate early diagnosis of graft dysfunction.
Subject(s)
Interleukin-8/biosynthesis , Lung/metabolism , Reperfusion Injury/metabolism , Animals , Interleukin-8/analysis , Lung/pathology , Neutrophils , Rabbits , Reperfusion Injury/pathologyABSTRACT
Objetivo: La generación local de citocinas es un factor patogénico en el daño por isquemia-reperfusión en la disfunción precoz del injerto. Este estudio analiza la expresión en tejido pulmonar de ARN mensajero de interleucina-8 (ARNm de IL-8) y su relación con los cambios intersticiales pulmonares en un modelo experimental de isquemia-reperfusión pulmonar normotérmica. Material y métodos: Se estudiaron 16 conejos de la raza Nueva Zelanda en 3 grupos de estudio: a) basal; b) isquemia (lóbulo inferior derecho tras isquemia de 1, 2 o 3 h), y c) reperfusión (lóbulos superior y medio derechos tras 1 h de isquemia y 1, 2 o 3 h de reperfusión). Se determinó la expresión del ARNm de IL-8 mediante transcripción inversa y reacción en cadena de la polimerasa y estudió la infiltración intersticial por polimorfonucleares (PMN). Para el análisis estadístico se empleó el test de la U de Mann-Whitney aceptando como significativo un valor de p < 0,05. Resultados: Durante el período de isquemia se observó respecto al basal elevación del ARNm de IL-8 al final de la primera hora (p = 0,009), pero no durante el resto del período isquémico. Los cambios intersticiales fueron mínimos. Durante la reperfusión los valores de ARNm de IL-8 fueron semejantes a los observados durante la isquemia, con una ligera elevación al final de segunda hora; no hubo diferencias significativas entre la primera, segunda y tercera horas. Hubo reclutamiento de PMN al inicio de la reperfusión (p = 0,014), sin observarse diferencias significativas en la segunda y tercera horas. Se objetivó un engrosamiento progresivo de los tabiques interalveolares y edema. Conclusiones: Los cambios en la expresión del ARNm de IL-8 durante la isquemia preceden a la infiltración intersticial de PMN durante la reperfusión, lo que señala una relación entre ambos procesos. La cuantificación del ARNm de IL-8 podría ser un procedimiento para el seguimiento diagnóstico de la disfunción precoz del injerto
Objective: Local cytokine production is a pathogenic factor in ischemiareperfusion injury in early graft dysfunction. This study analyzed interleukin 8 (IL-8) messenger RNA (mRNA) expression in lung tissue and the association between IL-8 mRNA levels and interstitial lung changes in an experimental model of warm lung ischemiareperfusion. Material and methods: We studied 16 New Zealand rabbits divided into 3 groups: control, ischemia (tissue taken from right lower lobe after 1, 2, or 3 hours of ischemia), and reperfusion (tissue taken from right upper and middle lobes after 1 hour of ischemia and 1, 2, or 3 hours of reperfusion). Expression of IL-8 mRNA was determined by reverse transcription and polymerase chain reaction. Interstitial infiltration by polymorphonuclear neutrophils was determined. The MannWhitney U-test was used for statistical comparisons, with P<.05 considered to indicate a significant result. Results: During ischemia, IL-8 mRNA levels were elevated at the end of hour 1 (P=.009) with respect to the control group, but not thereafter. Interstitial changes were minimal. IL-8 mRNA levels during reperfusion were similar to those observed during ischemia, with a slight increase at the end of hour 2. There were no significant differences between hours 1, 2, and 3. Polymorphonuclear neutrophil recruitment occurred at the beginning of reperfusion (P=.014), but no significant differences were observed at hours 2 or 3. Progressive thickening of alveolar septa and edema was documented. Conclusions: Changes in IL-8 mRNA expression during ischemia precede interstitial infiltration by polymorphonuclear neutrophils during reperfusion, suggesting that the 2 processes are related. Quantification of IL-8 mRNA expression could facilitate early diagnosis of graft dysfunction
