Interleukin-15 modulates interferon-γ and β-chemokine production in patients with HIV infection: implications for immune-based therapy

Interleukin (IL)-15 is a cytokine that has lymphocyte stimulatory activity similar to that of IL-2, and plays important immunoregulatory functions during HIV disease. To evaluate the role of IL-15 in HIV infection the following patients were studied: 18 antiretroviral-naive patients with advanced disease; 19 patients with continuous viral suppression and immunological response after 48–120 weeks of highly active antiretroviral therapy (HAART); and 12 patients with evidence of virological and immunological HAART treatment failure. Nineteen healthy blood donors were included as controls. The production of IL-15 by human peripheral blood monocytes stimulated with lipopolysaccharide and Mycobacterium avium complex, the priming effect of IL-15 on IFN-γ production from purified CD4 + and CD8 + T cells, and the ability of IL-15 to stimulate the β-chemokine release from purified CD4 + and CD8 + T cells were analyzed. In the present work IL-15 production by human peripheral blood monocytes was significantly increased in HIV-infected patients with long-term virological and immunological response to HAART. IL-15 enhanced the in vitro priming of CD4 + and CD8 + T cells for IFN-γ production, also in patients receiving HAART. Finally, IL-15 had positive effects on RANTES, MIP-1α, and MIP-1β release by CD4 + and CD8 + T cells. In conclusion IL-15 could affect the immune response of HIV-infected patients by augmenting and/or modulating IFN-γ production and β-chemokine release. These data about functional properties of IL-15 could provide new implications for immune-based therapies in HIV infection.