Anti-Inflammatory Effect of Caffeine Is Associated with Improved Lung Function after Lipopolysaccharide-Induced Amnionitis

Abstract

Background: Although caffeine enhances respiratory control and decreases the need for mechanical ventilation and resultant bronchopulmonary dysplasia, it may also have anti-inflammatory properties in protecting lung function. Objective: We hypothesized that caffeine improves respiratory function via an anti-inflammatory effect in lungs of a lipopolysaccharide (LPS)-induced pro-inflammatory amnionitis rat pup model. Methods: Caffeine was given orally (10 mg/kg/day) from postnatal day (p)1 to p14 to pups exposed to intra-amniotic LPS or normal saline. Expression of IL-1β was assessed in lung homogenates at p8 and p14, and respiratory system resistance (R_rs) and compliance (C_rs) as well as CD68 cell counts and radial alveolar counts were assessed at p8. Results: In LPS-exposed rats, IL-1β and CD68 cell counts both increased at p8 compared to normal saline controls. These increases in pro-inflammatory markers were no longer present in caffeine-treated LPS-exposed pups. R_rs was higher in LPS-exposed pups (4.7 ± 0.9 cm H₂O/ml·s) at p8 versus controls (1.6 ± 0.3 cm H₂O/ml·s, p < 0.01). LPS-exposed pups no longer exhibited a significant increase in R_rs (2.8 ± 0.5 cm H₂O/ml·s) after caffeine. C_rs did not differ significantly between groups, although radial alveolar counts were lower in both groups of LPS-exposed pups. Conclusions: Caffeine promotes anti-inflammatory effects in the immature lung of prenatal LPS-exposed rat pups associated with improvement of R_rs, suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism.