Sublethal Endotoxemia Promotes Pulmonary Cytokine-Induced Neutrophil Chemoattractant Expression and Neutrophil Recruitment but Not Overt Lung Injury in Neonatal Rats

Abstract

Gram-negative sepsis and septic shock remain major causes of morbidity and mortality in the newborn. Respiratory failure is a common feature in neonatal sepsis regardless of the presence or absence of associated pneumonia. In adult animal models, cytokine-induced neutrophil chemoattractant (CINC) is a potent chemoattractant for neutrophils and believed to play a role in endotoxin-induced lung injury. We examined this in a neonatal model. Ten-day-old Sprague-Dawley rats were injected with Salmonella enteritidis endotoxin (ETX) 0.03 mg/kg i.p. and sacrificed at baseline, 30 min, 1, 2, 4, 8 and 16 h post-ETX. Blood was collected by cardiac puncture. After bronchoalveolar lavage, lung tissue was collected and evaluated for neutrophil (polymorphonuclear leukocyte) recruitment by myeloperoxidase assay (MPO). Lung CINC expression was measured by Northern blot and ELISA. Peripheral blood leukocytosis was noted at 1 h (p < 0.001) with counts below baseline at 2 and 4 h. Differential counts revealed neutrophilia at 8 h (p < 0.001). MPO revealed pulmonary PMN recruitment peaking at 1 h (p < 0.05) and CINC RNA and protein expression peaked slightly later at 2 h (p < 0.001). No overt lung injury was noted by bronchoalveolar lavage cell counts or by histology. Therefore, pulmonary CINC expression and neutrophil recruitment follows LPS exposure in neonatal rats. This may represent priming of the lung tissue and a secondary event may be necessary for injury to occur

Importância da presença de granulações tóxicas para o diagnóstico hematológico de septicemia

“…Assim, neste estudo nós também submetemos estes dados (Gráfico 3 e Tabela 3) a uma análise estatística para verificação de sua associação com o diagnóstico de septicemia, através de comprovação por hemocultura positiva, a qual demonstrou significância estatística para os achados de leucocitose (70%) e desvio à esquerda (68%) com hemoculturas positivas, dados corroborados por outros autores na literatura. [1][2][3][4][5]8,9,10,13,14,15,18,19 Com esta análise tendo sido submetida a uma correção estatística, onde P foi multiplicado por cinco (o que corresponde ao número de categorias analisadas). Quando, por sua vez, investigamos a associação entre pacientes internados em UTI e a positividade de suas respectivas hemoculturas (Gráfico 4 e Tabela 4), observamos que, nos pacientes internados em UTI, as porcenta- A verificação da presença de hemoculturas positivas em pacientes não neonatos e pacientes neonatos (Gráfico 5 e Tabela 5), em nosso estudo, demonstrou que a porcentagem de hemoculturas positivas em pacientes não neonatos foi bem inferior (25%) que a porcentagem de hemoculturas positivas em pacientes neonatos (56%).…”

Modelling Bronchopulmonary Dysplasia in Animals: Arguments for the Preterm Rabbit Model

“…Although controversial some authors also suggest a link between patent ductus arteriosus and BPD [80]. These clinically relevant risk factors have occasionally been studied in animal models as well [81][82][83][84].…”

Postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia

“…In a systemic Gram‐negative sepsis (Salmonella endotoxin) neonatal (10 days) rat model, there was increased pulmonary neutrophil recruitment at 1 hr and expression of cytokine‐induced neutrophil chemoattractant (CINC) at 2 hr, but with no overt lung injury (up to 16 hr) (Tillema et al, ). However, in a 6 day neonatal rat model intratracheally exposed to LPS, there was increased neutrophil accumulation in the lungs at 24 hr, which changed to mostly macrophages at 15 day (Franco et al, ).…”