title: Kinetics and functional implications of Th1 and Th2 cytokine production following activation of peripheral blood mononuclear cells in primary culture.
abstract: The importance of cytokine production in some disease processes is now widely recognized. To investigate temporal relationships between cytokines, we stimulated peripheral blood mononuclear cells (PBMC) in vitro using the T cell mitogen phytohemagglutinin (PHA) and various antigens chosen to induce predominantly Th1 (streptokinase: streptodornase or purified protein derivative) or Th2 (Dermatophagoides pteronyssinus, bee or wasp venom: allergens in sensitive subjects) responses. Cytokine production was measured by sensitive bioassays or enzyme-linked immunosorbent assays. Of the 30 subjects studied, 10 were normal and 20 individuals were allergic to either D. pteronyssinus (n = 10) or bee venom (n = 10) (examined before specific allergen immunotherapy). We examined the temporal profiles of a panel of cytokines produced in primary culture. In PHA-driven cultures, cytokines were found to be sequentially produced in the order interleukin (IL)-2, IL-4, IL-5, IL-3, interferon (IFN)-gamma, IL-10, IL-6, IL-12 and tumor necrosis factor (TNF)-alpha. The response to allergen in allergic patients was predominantly Th2 in nature, with the production of IL-4, IL-5, IL-6 and IL-10, but little or no IFN-gamma. IL-2, IL-3, TNF-alpha and IL-12 were also produced in low amounts. The response of both atopic and normal subjects to recall bacterial antigens was predominantly Th1, with high levels of IFN-gamma, IL-2 and TNF-alpha. The relevance of the order, amount and speed of production, characteristic kinetics (production, consumption, homeostatic regulation) and the cell source of the cytokines are discussed.
authors.affiliation: Molecular Immunopathology Unit, Medical Research Council Centre, Cambridge, GB.
authors.forename: S
authors.initials: S
authors.lastname: McHugh
authors.forename: J
authors.initials: J
authors.lastname: Deighton
authors.forename: I
authors.initials: I
authors.lastname: Rifkin
authors.forename: P
authors.initials: P
authors.lastname: Ewan
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001514:Bee Venoms / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004391:Dust; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D008925:Mites / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors
chemical_list: D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; D004391:Dust; D008934:Mitogens