Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells.
BACKGROUND
Vitamin C (ascorbic acid) is an essential water-soluble antioxidant in cells and plasma. Besides metabolic functions, vitamin C is also known to contribute to immune homeostasis. Recently, it has been demonstrated that vitamin C has an inhibitory effect on the expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in adult whole blood cells in vitro. It has been postulated that vitamin C might be an interesting compound for modulation of an over-exuberant immune response, e.g., in patient cohorts susceptible for the development of systemic inflammatory response syndrome such as neonates. It was the aim of this study to investigate the modulatory effects of vitamin C on the production of inflammatory mediators in neonatal cord blood cells.


METHODS
The intracytoplasmic production of pro-inflammatory cytokines in neonatal cord blood cells stimulated with lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin was assessed by flow-cytometry.


RESULTS
In contrast to our previous observations from adult whole blood cells, 20 mM vitamin C mildly stimulated the percentage of neonatal monocytes producing IL-6 after lipopolysaccharide stimulation (e.g., 11.3% increase compared to control, p = 0.005). In the presence of 20 mM vitamin C, even a stronger stimulatory effect was noted for the percentage of IL-8 (e.g., 46.7% increase, p < 0.001) and TNF-alpha producing neonatal monocytes (e.g., 69.2% increase, p = 0.004; n = 20). In accordance with adult data, the percentage of neonatal lymphocytes producing IL-2 after phorbol 12-myristate 13-acetate/ionomycin stimulation was dose-dependently reduced (e.g., 41.3% inhibition, p = 0.001, 20 mM vitamin C), while the percentage of TNF-alpha producing lymphocytes was mildly stimulated (e.g., 20.8% increase, p = 0.003, 20 mM vitamin C).


CONCLUSIONS
Interestingly, vitamin C was demonstrated to enhance pro-inflammatory responses in CD14(+) cord blood cells while only intracellular IL-2 production in CD3(+) cells was diminished. These data suggest that vitamin C differentially influences intracytoplasmic cytokine production in adults and neonates, and further studies are needed to elucidate the underlying mechanisms of this selective immunomodulation.
Hartel
Christoph
C
Department of Pediatrics, University of Lubeck Medical School, Lubeck, Germany.
Puzik
Alexander
A
Gopel
Wolfgang
W
Temming
Petra
P
Bucsky
Peter
P
Schultz
Christian
C
D001205:Ascorbic Acid / Q000276:immunology / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003593:Cytoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007155:Immunologic Factors / Q000494:pharmacology*; D007231:Infant, Newborn / Q000097:blood*; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects
D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D007376:Interleukin-2; D001205:Ascorbic Acid