title: The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype.
abstract: The production of inflammatory mediators, relevant to (auto)immune diseases and chronic inflammatory conditions, can be modulated by dietary intake of n-3 and n-6 long chain polyunsaturated fatty acids (PUFAs). It was suggested that these effects are related to the formation of different series of eicosanoids, in particular prostaglandin-E (PGE). In this study we investigated whether prostaglandin subtypes metabolized from arachidonic acid (PGE2), dihomo-gamma-linolenic acid (PGE1) or eicosapentaenoic acid (PGE3) have different effects on T-cell proliferation and cytokine production in vitro. Freshly isolated human peripheral blood mononuclear cells (PBMC) were stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the presence or absence of exogenous PGE1, PGE2 or PGE3. We found that tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and to a lesser extent interleukin (IL)-10 production was inhibited by all PGE-subtypes in ConA-stimulated PBMC concomitant with unaffected IL-2 levels. The modulated cytokine production of ConA stimulated cells was independent of T-cell proliferation. PGE2 and PGE1 moderately stimulated proliferation, while PGE3 inhibited the proliferative response to some extent. In LPS-stimulated PBMC, TNF-alpha production was inhibited by all PGE-subtypes, whereas IL-6 remained unaffected and IL-10 production was increased. Time course experiments on the effects of PGE-subtypes on cytokine production after ConA or LPS stimulation showed these effects to be time dependent, but indifferent of the prostaglandin subtype added. Overall, the modulatory effects of PGE on cytokine production were irrespective of the subtype. This may implicate that the immunomodulatory effects of PUFAs, with respect to cytokine production, are not caused by a shift in the subtype of PGE.
authors.affiliation: Department of Condition and Disease Specific Research, Numico Research B.V., Wageningen, The Netherlands.
authors.forename: Maaike M B W
authors.initials: MM
authors.lastname: Dooper
authors.forename: Lianne
authors.initials: L
authors.lastname: Wassink
authors.forename: Laura
authors.initials: L
authors.lastname: M'Rabet
authors.forename: Yvo M F
authors.initials: YM
authors.lastname: Graus
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D015232:Dinoprostone / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D011458:Prostaglandins E / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007378:Interleukins; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; C033246:prostaglandin E3; D007371:Interferon-gamma; D000527:Alprostadil; D015232:Dinoprostone