No abstract

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown.The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia.In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (10 6 cfu?mL -1 ) was bronchoscopically inoculated.The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue.In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

An abnormal inflammatory response (IR) in pneumonia is associated with poor outcomes and high mortality. Animal models could help to better understand the relationship between the pulmonary infection and the associated IR. The aims of the present study were to validate an experimental model of pneumonia induced by the inoculation of Pseudomonas aeruginosa in ventilated piglets and to study the associated IR over a long period of time (96 h).Five Lagerwhite-Landrace piglets were ventilated for 4 days. After intubation, a solution containing 75 mL of P. aeruginosa (10 6 colony-forming units?mL) was bronchoscopically inoculated. Physiological and laboratory parameters were monitored throughout the study. Proinflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed.All the animals developed histopathological evidence of pneumonia. Microbiological studies of both BAL and lung confirmed the presence of P. aeruginosa in all the samples. Throughout the study, an increase in interleukin-6 was observed in serum and in BAL.In conclusion, the experimental model of pneumonia induced by the inoculation of high concentrations of Pseudomonas aeruginosa in ventilated piglets is feasible and could be appropriate for the evaluation of different aspects of the associated inflammatory response.

Ventilator-associated pneumonia (VAP) is the leading cause of death in critically ill patients in intensive care units. In the last 20 years, different animal models have been a valuable tool for the study of pathophysiology and phenotypic characteristics of different lung infections observed in humans, becoming an essential link between '''' testing and clinical studies. Different animal models have been used to study the mechanism of a deregulated inflammatory response and host tissue damage of sepsis in VAP, as well as different infection parameters such as clinical, physiological, microbiological and pathological facts in several large and small mammals. In addition, the dosage of inflammatory modulators and their consequences in local and systemic inflammation, or even the administration of antibiotics, have been evaluated with very interesting results. Although some bronchial inoculation ways do not resemble the common pathophysiologic mechanisms, the experimental model of VAP induced by the inoculation of high concentrations of pathogens in mechanically ventilated animals is useful for studying the local and systemic responses of sepsis in VAP and it reproduces biological mechanisms such as acute lung injury, distress response, cardiac events and immune modulation comparable with clinical studies.