Dietary nucleotides and human immune cells. II. Modulation of PBMC growth and cytokine secretion.
OBJECTIVE
The immune system is dependent on purines and pyrimidines as building blocks for DNA and RNA synthesis to enable rapid cell proliferation and protein synthesis. Emerging evidence suggests that dietary nucleotides optimize immune function. We investigated whether growth and function of human immune cells were affected by an exogenous source of nucleotides during specific antigen challenge.


METHODS
Peripheral blood mononuclear cells from healthy individuals (n = 10) were stimulated with influenza virus antigen and DNA-Na+ from fish soft roe, RNA from bakers yeast (Saccharomyces cerevisiae), 2'deoxyadenosine 5'-monophosphate sodium, 2'deoxycytidine 5'-monophosphate sodium, 2'deoxyguanosine 5'-monophosphate sodium, or 2'deoxyuridine 5'-monophosphate disodium. Growth effects were ascertained by measuring the amount of tritium-labeled Thymidine 5'-monophosphate sodium incorporated into cell DNA. Cell function was measured by detection of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and interleukin-10 production.


RESULTS
Specific nucleotide derivatives alone did not affect the growth of healthy peripheral blood mononuclear cells. However, the nucleotide derivatives influenced immune cell growth and cytokine secretion when cocultured with specific antigen. DNA, RNA, deoxyadenosine monophosphate, deoxycytidine monophosphate, and deoxyuridine monophosphate increased influenza virus antigen-induced immune cell proliferation. In contrast, deoxyadenosine monophosphate and thymosine monophosphate inhibited the antigen-induced growth response. RNA and deoxyadenosine monophosphate cocultured with virus antigen significantly increased peripheral blood mononuclear cell secretion of IFN-gamma, interleukin-10, and tumor necrosis factor-alpha. DNA increased virus antigen-induced immune cell secretion of IFN-gamma only, whereas deoxyuridine monophosphate significantly increased secretion of interleukin-10 only. Deoxyguanosine monophosphate completely inhibited virus-triggered IFN-gamma secretion, whereas thymosine monophosphate did not change the secretion pattern of measured cytokines.


CONCLUSIONS
Nucleotide derivatives affect growth and function of specific virus antigen-stimulated human immune cells in vitro.
Holen
Elisabeth
E
Broegelmann Research Laboratory, University of Bergen, Bergen, Norway. eho@nifes.no
Bjørge
Oddvin A
OA
Jonsson
Roland
R
D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009711:Nucleotides / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D009975:Orthomyxoviridae / Q000276:immunology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000956:Antigens, Viral; D016207:Cytokines; D009711:Nucleotides; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D016753:Interleukin-10; D007371:Interferon-gamma