Caffeine modulates TNF-α production by cord blood monocytes: The role of adenosine receptors

Raul Chavez-Valdez, Marsha Wills-Karp, Rajni Ahlawat, Elizabeth A. Cristofalo, Amy Nathan, Estelle B Gauda

Research output: Contribution to journalArticlepeer-review


Caffeine, a nonspecific adenosine receptor (AR) antagonist is widely used to treat apnea of prematurity. Because adenosine modulates multiple biologic processes including inflammation, we hypothesized that AR blockade by caffeine would increase cytokine release from neonatal monocytes. Using cord blood monocytes (CBM), we investigated 1) the changes in AR mRNA profile by real time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and protein expression (western blot) after in vitro culture, caffeine or lipopolysaccharide (LPS) exposure, and 2) the modulation of cytokine release and cyclic adenosine monophosphate (cAMP) production by enzyme-linked immunosorbent assay (ELISA) induced by caffeine and specific AR antagonists: DPCPX(A 1R), ZM241385(A2aR), MRS1754(A2bR), and MRS1220(A3R). After 48 h in culture, A2aR and A 2bR gene expression increased 1.9 (p = 0.04) and 2.5-fold (p = 0.003), respectively. A1R protein expression directly correlated with increasing LPS concentrations (p = 0.01), with minimal expression preexposure. Only caffeine (50 μMu) and DPCPX (10 nM) decreased tumor necrosis factor-alpha (TNF-α) release from LPS activated-CBM by 20 and 25% (p = 0.01) and TNF-α gene expression by 30 and 50%, respectively, in conjunction with a ≥2-fold increase in cAMP (p < 0.05). AR blockade did not modulate other measured cytokines. The induction of A1R after LPS exposure suggests an important role of this receptor in the control of inflammation in neonates. Our findings also suggest that caffeine, via A 1R blockade, increases cAMP production and inhibits pretranscriptional TNF-a production by CBM.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalPediatric research
Issue number2
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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