Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis

Neonatology. 2014;106(3):235-40. doi: 10.1159/000363217. Epub 2014 Jul 5.


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 (Rrs) and compliance (Crs) 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. Rrs 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 Rrs (2.8 ± 0.5 cm H2O/ml·s) after caffeine. Crs 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 Rrs, suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents / pharmacology*
  • Caffeine / pharmacology*
  • Chorioamnionitis* / chemically induced
  • Disease Models, Animal
  • Female
  • Lipopolysaccharides
  • Lung / drug effects*
  • Lung / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Physiological Phenomena / drug effects


  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Caffeine