ExperimentalPseudomonas aeruginosapneumonia: evaluation of the associated inflammatory response

Abstract

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.

Effects of glucocorticoids in ventilated piglets with severe pneumonia

“…methylprednisolone 0.5 mg?kg -1 every 12 h; CIP+GC group). In keeping with the present research protocol, piglets of each group were under mechanical ventilation for 84 h [28]. Piglets that died in the first 12 h were excluded from the study.…”

“…The piglets were then placed in a prone position and were mechanically ventilated for 4 days. Ventilator parameters consisted of tidal volume (VT) of 10 mL?kg -1 , a respiratory frequency of 15 breaths?min -1 , an inspiratory time of 33%, with an inspiratory oxygen fraction (FI,O 2 ) of 100% and a positive end-expiratory pressure of 0, as described previously [28].…”

“…This model closely resembles human pneumonia and has proven to be very useful for evaluating different aspects related to the diagnosis and treatment of severe pneumonia [21][22][23][24][25][26][27]. Using this animal model, severe pneumonia was reproduced and the associated inflammatory response was studied after inoculation with high concentrations of Pseudomonas aeruginosa [28], the most lethal causative microorganism, both in CAP and ventilator-associated pneumonia [2,8,29].…”

Corticosteroids in severe pneumonia: Table 1—

“…Studies concerning severe pneumonia have shown that, despite the inflammatory response initially being compartmentalised [9], an increase in inflammatory cytokine levels in serum is also detected and related to poor prognosis [10][11][12][13].…”

“…Although the intimal mechanisms by which the inflammatory response modulated by GCs can interfere with pulmonary infection are not well elucidated, in vitro studies and experimental work in animals have provided some clues regarding this issue. The present authors' group has developed an experimental model of Pseudomonas aeruginosa pneumonia in ventilated pigs [10], in which the effect of GCs has been studied by comparing three groups of animals with severe pneumonia (those without treatment, those with antibiotic treatment and those with antibiotic treatment plus GCs). In this model, pigs treated with antibiotics plus GCs experienced, after 96 h of pneumonia onset, a decrease in the local inflammatory response compared to the other groups.…”