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Published on: August 7, 2017
Correlation between serum caffeine levels and changes in cytokine profile in a cohort of preterm infants
Raul Chavez Valdez1, Rajni Ahlawat, Marsha Wills-Karp
1Department of Pediatrics, Division of Neonatology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Insights
Caffeine treatment for preterm infants with apnea correlates with cytokine changes. Higher caffeine levels (≥ 20 μg/mL) are linked to a proinflammatory cytokine profile after one week.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Immunology
Background:
- Apnea of prematurity is common in preterm infants.
- Caffeine is a standard treatment for apnea of prematurity.
- The impact of caffeine on infant cytokine profiles is not fully understood.
Purpose of the Study:
- To investigate the association between caffeine treatment and changes in cytokine levels in preterm infants.
- To determine if specific caffeine concentrations correlate with particular cytokine profiles.
Main Methods:
- Observational prospective study of 26 preterm infants (≤ 30 weeks gestational age).
- Cytokine profiles in peripheral blood and tracheal aspirates were measured using ELISA.
- Measurements were taken at birth, and at 24 hours and 1 week after initiating caffeine treatment.
Main Results:
- Interleukin-10 levels decreased significantly at 24 hours post-caffeine initiation.
- At 1 week, caffeine levels showed U-shaped correlations with pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and an inverse linear correlation with anti-inflammatory IL-10.
- Serum caffeine levels ≥ 20 μg/mL were associated with a proinflammatory cytokine profile after 1 week.
Conclusions:
- Caffeine treatment for apnea of prematurity is associated with alterations in the infant cytokine profile.
- Elevated caffeine levels (≥ 20 μg/mL) in preterm infants correlate with a proinflammatory state after one week of treatment.
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.
