Background: Proinflammatory cytokines are associated with increased risk of chronic lung disease in premature patients. Chorioamnionitis as well as mechanical ventilation have been shown to increase cytokine expression in lung tissue and blood. Objective: To test the hypothesis that low-dose LPS exposure would modify the cytokine response to HTVV in newborn rats.
Methods: Newborn (3-6 days) rats were randomly assigned to four groups (I-IV: 12-14 animals/group). Group III and IV were injected 24h prior ventilation with 3 mg LPS/kg while I and II received saline. Group II and IV were subjected to HTVV (25ml/kg, 60/min, 3h). Lung IL-6, MIP-2, IL-1beta and TNF-alpha mRNA was determined by realtime RT-PCR. Cytokine protein content was measured in bronchoalveolar lavage fluid (BALF). Statistical analysis: one-way ANOVA and t-test (significance: p<0.05).
Results: LPS injection reduced weight gain within the 24h following injection from 17.9% (saline) to 11.4% (p<0.05). Pre-treatment with LPS did neither affect lung compliance nor blood gas values. LPS alone did not change cytokine expression. In contrast, HTVV alone increased mRNA expression of IL-6 by 7.2 fold, MIP-2 by 7.9 fold and IL-1beta by 1.8 fold (p<0.05). The combination of HTVV and LPS further increased the expression of IL-6 (II vs IV; 10.5 fold) and IL-1beta (II vs IV; 2.3 fold). IL-6 protein content in BALF increased with HTVV and LPS+HTVV treatments (I 19.4, II 34.0, III 17.5, IV 43.7 pg/ml).
Conclusions: Whereas low grade systemic inflammation alone does not change the proinflammatory cytokine expression, its combination with HTVV potentiates the proinflammatory cytokine response in the newborn lung. Therefore, we speculate that newborn patients born in a context of chorioamnionitis are at higher risk to develop ventilator associated lung injury than those without association with inflammation/infection.