title: Potentiation of cytokine-induced proliferation of human Natural Killer cells by intravenous immunoglobulin G.
abstract: Intravenous IgG (IVIG) therapy can be used for immunomodulation. IL-2 is an immunoregulatory cytokine. We evaluated IVIG modulation of human blood lymphocyte response to IL-2 and other cytokines. Neither IVIG nor low concentrations of IL-2 (3-30U/ml) induced lymphocyte proliferation, but in combination they synergistically enhanced proliferation of NK cells. The CD56(bright) cells expanded more than CD56(dim) NK cells, with 90% of NK cells dividing up to 8 generations by day 6, while <8% of T cells divided. IVIG also potentiated NK cell proliferation with IL-12, IL-15 and IL-18. The IVIG+cytokine-expanded NK cells were less cytotoxic for K562 cells, than NK cells with cytokine alone. IVIG also enhanced interferon-γ production with IL-2, IL-12 and IL-18. In conclusion, IVIG selectively potentiates NK cell proliferation and interferon-γ secretion with IL-2, IL-12, IL-15 and IL-18 in vitro. These findings warrant evaluation in vivo in relation to NK cells and the immunoregulatory actions of IVIG.
authors: Departments of Pediatrics, Dalhousie University, Halifax, NS, Canada. Electronic address: andrew.issekutz@iwk.nshealth.ca.
authors: Andrew C
authors: AC
authors: Issekutz
authors: Departments of Pediatrics, Dalhousie University, Halifax, NS, Canada.
authors: Beata
authors: B
authors: Derfalvi
authors: CSL Behring Research and Development, Bern, Switzerland.
authors: Fabian
authors: F
authors: Käsermann
authors: Departments of Pediatrics, Dalhousie University, Halifax, NS, Canada.
authors: Derek
authors: D
authors: Rowter
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D019409:Interleukin-15; D020382:Interleukin-18; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Cytokine; IgG; Immunomodulation; NK lymphocyte; Natural killer cell