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.
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.
Lucey
D R
DR
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Pinto
L A
LA
Bethke
F R
FR
Rusnak
J
J
Melcher
G P
GP
Hashemi
F N
FN
Landay
A L
AL
Kessler
H A
HA
Paxton
R J
RJ
Grabstein
K
K
Shearer
G M
GM
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
D019409:Interleukin-15; D007376:Interleukin-2; D007371:Interferon-gamma