Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants

Objective: To determine changes in cytokine levels associated with caffeine treatment in a cohort of preterm infants.

Study design: 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.