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

A depressed level of natural killer (NK) activity is one of the various imm unologic abnormalities in human immunodeficiency virus (HIV) infection. Int erleukin-15 (IL-15), an immunotherapeutic candidate in HIV infection, incre ases NK activity and induces the excretion of CC-chemokines from divergent immune cells, but the mechanisms of NK activity enhancement by IL-15 stimul ation is not clearly established in HIV infection. This study examined whet her CC-chemokines, which are known to increase NK activity, are secreted ad equately in HIV-infected individuals, and also investigated whet her P-glyc oprotein is involved in NK activity enhancement after IL-15 administration. NE: 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 se crete CC-chemokines, such as, macrophage inflammatory protein-1 alpha (MIP- 1 alpha), macrophage chemotactic protein-1 (MCP-1) and regulated upon activ ation, normal T cells expressed and secreted (RANTES) in both HIV-infected individuals and controls with no significant difference. P-glycoprotein exp ression and function is decreased in HIV-infected individuals and restored only in NK cells of HIV-infected individuals after IL-15 stimulation. P-gly coprocein may play a role in the mechanism of increased NK cell activity in HIV-infected individuals after IL-15 stimulation.