title: Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants.
abstract: OBJECTIVE
  To determine changes in cytokine levels associated with caffeine treatment in a cohort of preterm infants.
  
  
  METHODS
  For this observational prospective study, we collected clinical data from 26 preterm infants (≤ 30 weeks gestational age). In addition to caffeine levels, cytokine profiles in peripheral blood (PB) and tracheal aspirates (TA) were determined with enzyme-linked immunosorbent assay at birth, before and after (at 24 hours and 1 week) initiation of caffeine. Non-parametric statistics were applied.
  
  
  RESULTS
  Included infants were 26.9 ± 1.7 weeks gestational age and weighed 985 ± 202 g. At birth, all cytokine concentrations were significantly greater in TA than PB. Serum caffeine levels were 11.1 μg/mL (interquartile range, 1.85) at approximately 24 hours post-load and 16.4 (8.7) μg/mL at 1 week on treatment. At approximately 24 hours post-load, interleukin (IL)-10 levels decreased by 47.5% (P = .01) in PB and 38.5% (P = .03) in TA, whereas other cytokine levels remained unchanged. At 1 week, caffeine levels were correlated (U-shaped) with changes in proinflammatory tumor necrosis factor-α (R(2) = 0.65; P = .0008), interleukin (IL)-1β (R(2) = 0.73; P = .0007), and IL-6 (R(2) = 0.59; P = .003), whereas inversely correlated (linear) with the anti-inflammatory IL-10 (R(2) = 0.64; P = .0008). Altogether, caffeine, at serum levels ≥ 20 μg/mL, was associated with a proinflammatory profile after 1 week of treatment.
  
  
  CONCLUSIONS
  Caffeine treatment for apnea of prematurity correlates with changes in cytokine profile. Caffeine levels ≥ 20 μg/mL are associated with a proinflammatory profile in our cohort of preterm infants.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Chavez Valdez
authors.forename: Rajni
authors.initials: R
authors.lastname: Ahlawat
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Amy
authors.initials: A
authors.lastname: Nathan
authors.forename: Tarrah
authors.initials: T
authors.lastname: Ezell
authors.forename: Estelle B
authors.initials: EB
authors.lastname: Gauda
mesh_terms: D002110:Caffeine / Q000097:blood*; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008297:Male; D011446:Prospective Studies
chemical_list: D016207:Cytokines; D002110:Caffeine