Pharmacological modulation with prolonged administration of moderate doses of steroid in a murine model of septic acute lung injury after burn insult

Introduction

Many patients who experience surgical stress including burn injury become susceptible to severe sepsis and septic organ dysfunction including acute lung injury (ALI), which remains the primary contributor to morbidity and mortality in burn patients. Proinflammatory cytokines including several chemokines are implicated in this process. The pharmacological modulation with steroid inhibiting the process of cytokine synthesis may serve as effective therapy for the prevention of tissue injury and the resultant organ dysfunction including respiratory failure. We developed a murine model of septic ALI after burn insult and examined the effects of prolonged administration of moderate doses of steroid.

Methods

Male BALB/c mice were divided into three groups. Group I served for sham burns. In groups II and III, a 15% BSA full-thickness burn was made on the dorsum under ether anesthesia, followed by adequate fluid resuscitation. After the burn injury, 3 mg/kg prednisolone (PSL) in group III was administered subcutaneously daily for 10 days. On the 11th day, 10 mg/kg lipopolysaccharide (LPS) was injected intravenously. In the first experiment, we observed the survival within 72 hours after LPS injection in each group (n = 10). In the second experiment, we sacrificed the animals at 12 hours after LPS injection, then obtained plasma and lung tissue to determine the levels of TNFα and macrophage inflammatory protein-2 (MIP-2, a functional homologue of human IL-8 in mice) in these samples (n = 8, sandwich ELISA). We also determined gene expression (n = 4, MIP-2/GAPDH mRNA ratio by RT-PCR), myeloperoxidase activities (MPO, n = 8) and histopathological findings in the lung tissue.

Results

The survival and production of cytokines are shown in Table 1. Histopathological findings in group III were obviously attenuated.

Table 1

Conclusion

In this animal model, a pretreatment with PSL as the cytokine synthesis inhibitor improved the survival and attenuated the production of cytokines. The complications associated with sepsis after burn insults, especially ALI, could be preventable by the pharmacological modulation with prolonged administration of moderate doses of steroid.