In vitro effects of eicosanoids derived from different 20-carbon fatty acids on T helper type 1 and T helper type 2 cytokine production in human whole-blood cultures.
BACKGROUND
Different series prostaglandins (PGs) and leukotrienes (LTs) are synthesized from different 20 carbon fatty acid precursors. The effects of the different series of PGs and LTs on production of T helper type 1 (Th1) and Th2 cytokines by human cells are not well established.


OBJECTIVE
To characterize the influence of PGs and LTs produced from different fatty acid precursors on the Th1 and Th2 cytokine profile in mitogen-stimulated human whole-blood cultures.


METHODS
Blood from healthy adult males was diluted and cultured with concanavalin A in the presence or absence of a range of concentrations of various PGs or LTs. Cytokine concentrations in culture supernatants were analysed by enzyme-linked immunosorbent assay (ELISA).


RESULTS
PGE1, PGE2 and PGE3 significantly and dose-dependently decreased the concentrations of the Th1 cytokines IL-2 and IFN-gamma by up to 50% and 70%, respectively. The three PGs exhibited similar potency towards IFN-gamma production. At the highest concentration used (10-6 m) PGE1, but not PGE2 or PGE3, increased the concentration of the Th2 cytokine IL-4 by about 70%. IL-10 production was not affected by PGs. The ratio of the concentrations of IFN-gamma to IL-4 was significantly decreased at PGE concentrations of 10-7 and 10-6 M with all three PGEs having similar effects. LTB4, LTC4 and LTC5 did not significantly affect production of the cytokines studied.


CONCLUSIONS
PGE produced from different fatty acids significantly decrease Th1 cytokine production resulting in a shift in the Th1, Th2 balance in favour of a Th2 response. PGE produced from different fatty acid precursors are equipotent in their effects on human T lymphocytes. Thus, although changes in the pattern of dietary fatty intakes may contribute to the increased prevalence of atopic disease, this would probably not be mediated through substitution of one PGE with another from a different series. It may, however, be mediated through a change in the total amount of PGE produced at the site of antigen presentation.
Miles
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Institute of Human Nutrition, University of Southampton, Bassett Crescent East, Southampton, UK.
Aston
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Calder
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D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D015777:Eicosanoids / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D015289:Leukotrienes / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D016207:Cytokines; D015777:Eicosanoids; D007378:Interleukins; D015289:Leukotrienes; D011453:Prostaglandins; D011458:Prostaglandins E; D007371:Interferon-gamma