Restoration of P-glycoprotein function is involved in the increase of natural killer activity with exogenous interleukin-15 in human immunodeficiency virus-infected individuals.
A depressed level of natural killer (NK) activity is one of the various immunologic abnormalities in human immunodeficiency virus (HIV) infection. Interleukin-15 (IL-15), an immunotherapeutic candidate in HIV infection, increases NK activity and induces the excretion of CC-chemokines from divergent immune cells, but the mechanisms of NK activity enhancement by IL-15 stimulation is not clearly established in HIV infection. This study examined whether CC-chemokines, which are known to increase NK activity, are secreted adequately in HIV-infected individuals, and also investigated whether P-glycoprotein is involved in NK activity enhancement after IL-15 administration. NK activity increased with IL-15 stimulation in NK cells of HIV-infected individuals, as it does in normal NK cells. IL-15 stimulates NK cells to secrete CC-chemokines, such as, macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage chemotactic protein-1alpha (MCP-1alpha) and regulated upon activation, normal T cells expressed and secreted (RANTES) in both HIV-infected individuals and controls with no significant difference. P-glycoprotein expression and function is decreased in HIV-infected individuals and restored only in NK cells of HIV-infected individuals after IL-15 stimulation. P-glycoprotein may play a role in the mechanism of increased NK cell activity in HIV-infected individuals after IL-15 stimulation.
Chang
K H
KH
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Kim
J M
JM
Yoo
N C
NC
Kim
W H
WH
Park
J H
JH
Choi
I H
IH
Kim
H S
HS
Lee
K W
KW
Song
Y G
YG
Hong
S K
SK
Kim
H Y
HY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D015658:HIV Infections / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019409:Interleukin-15; D011994:Recombinant Proteins