title: In vitro immunologic and virologic effects of interleukin 15 on peripheral blood mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients.
abstract: Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional activity, such as T-cell and B-cell stimulation, with IL-2. The effect of IL-2 on immune function and human immunodeficiency virus (HIV) viral load in HIV-infected patients is being actively studied. Thus, we examined how IL-15 compares with IL-2 in several in vitro immunologic and virologic assays in order to explore whether a rationale exists for pursuing initial clinical therapeutic trials with IL-15. The effects of IL-15 on induction of lymphokine-activated killer (LAK) cells, gamma interferon (IFN-gamma) production from HIV-positive peripheral blood mononuclear cells (PBMCs), and HIV production from PBMCs were studied. Induction of LAK cells by IL-15 was found in eight of eight HIV-positive donors. Incubation of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on HIV replication in PBMCs from five HIV-positive patients and four HIV-negative donors whose PBMCs were infected in vitro with HIV. Levels of HIV p24 antigen were moderately lower in the presence of 10 ng of IL-15 per ml than with 10 ng of IL-2 per ml, but they were similar for 100 and 500 ng of each cytokine per ml. In summary, IL-15 can induce LAK cell activity in HIV-seropositive patients and can stimulate IFN-gamma production from PBMCs of some donors. IL-15 stimulates levels of HIV production from PBMCs which are similar to or moderately lower than those obtained with IL-2, depending on cytokine concentration.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Lucey
authors.forename: L A
authors.initials: LA
authors.lastname: Pinto
authors.forename: F R
authors.initials: FR
authors.lastname: Bethke
authors.forename: J
authors.initials: J
authors.lastname: Rusnak
authors.forename: G P
authors.initials: GP
authors.lastname: Melcher
authors.forename: F N
authors.initials: FN
authors.lastname: Hashemi
authors.forename: A L
authors.initials: AL
authors.lastname: Landay
authors.forename: H A
authors.initials: HA
authors.lastname: Kessler
authors.forename: R J
authors.initials: RJ
authors.lastname: Paxton
authors.forename: K
authors.initials: K
authors.lastname: Grabstein
authors.forename: G M
authors.initials: GM
authors.lastname: Shearer
mesh_terms: D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000032:analysis / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D007371:Interferon-gamma