title: 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 (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.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Ozge A
authors.initials: OA
authors.lastname: Köroğlu
authors.forename: Peter M
authors.initials: PM
authors.lastname: MacFarlane
authors.forename: Kannan V
authors.initials: KV
authors.lastname: Balan
authors.forename: Woineshet J
authors.initials: WJ
authors.lastname: Zenebe
authors.forename: Anjum
authors.initials: A
authors.lastname: Jafri
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Prabha
authors.initials: P
authors.lastname: Kc
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002821:Chorioamnionitis / Q000139:chemically induced; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012143:Respiratory Physiological Phenomena / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D002110:Caffeine