title: In vivo priming effects of interferon-beta ser on NK activity of peripheral blood mononuclear cells in cancer patients.
abstract: Natural killer (NK) activity was assayed in fresh peripheral blood mononuclear cells (PBMs) from cancer patients receiving interferon (IFN)-beta ser. Patients received a single intravenous injection of IFN-beta ser (90 x 10(6) IU m-2) on alternate days for 2 weeks, followed by a higher dose (180 x 10(6) IU m-2) on the same schedule. PBM NK lysis of K562 target cells was significantly increased in PBMs sampled 24 h after the initial injection (P < 0.05). At the end of the first 2 weeks of the protocol, NK cytotoxic activity of PBMs had fallen below the original baseline levels; the higher IFN dose subsequently given was without effect. However, significant increases in the proportion of CD16+ cells were seen following each injection. A positive correlation was also seen between the increased lytic activity of CD16+ NK cells and the proportion of CD38+ NK cells, but not the proportion of CD56+ NK cells. In vitro IFN-treatment of these in vivo-treated PBMs resulted in a further increase in NK activity. Pre-exposure in vivo to IFN-beta ser seems to prime the PBMs to respond to in vitro stimulation by IFN-gamma, which otherwise had no effect. Phenotypic analysis of PBMs after in vitro exposure to IFN-beta ser showed that the levels of CD16+, CD38+ and CD56+ cells did not change. All the NK activity responding to IFN-beta ser was found in the CD16+ enriched population of PBM, suggesting that it is unlikely that in vivo redistribution of CD16+ subsets representative of NK cells has occurred in the peripheral blood.
authors.affiliation: Section of Immunology, Childrens' Medical Research Center, National Children's Hospital, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimiya
authors.forename: R J
authors.initials: RJ
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Groveman
authors.forename: K
authors.initials: K
authors.lastname: Sielaff
authors.forename: T
authors.initials: T
authors.lastname: Kohsaka
authors.forename: M
authors.initials: M
authors.lastname: Nakayama
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000097:blood; D019002:CD56 Antigen / Q000097:blood; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000008:administration & dosage; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000097:blood; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D019002:CD56 Antigen; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007371:Interferon-gamma; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D000068556:Interferon beta-1a