Yonsei Med J.  2000 Oct;41(5):600-606. 10.3349/ymj.2000.41.5.600.

Restoration of P-glycoprotein function is involved in the increase of natural killer activity with exogenous interleukin-15 in human immunodeficiency virus-infected individuals

Affiliations
  • 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. jmkim@yumc.yonsei. ac.kr
  • 2Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
  • 3Department of Clinical Pathology, Yonsei University College of Medicine, Seoul, Korea.

Abstract

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.

Keyword

Interleukin-15; NK cells; NK activity; HIV; P-glycoprotein

MeSH Terms

HIV Infections/physiopathology*
HIV Infections/pathology
Human
Interleukin-15/pharmacology*
Killer Cells, Natural/physiology*
Killer Cells, Natural/drug effects*
P-Glycoprotein/physiology*
Recombinant Proteins/pharmacology
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