Interleukin-15 in HIV infection: immunological and virological interactions in anti retroviral-naive and -treated patients

Objective: To investigate the immunological and virological interactions between interleukin (IL)-15 and HIV in antiretroviral-naive and highly active antiretroviral therapy (HAART)-treated patients. Design: Three groups of HIV-infected patients were studied: 20 untreated patients with advanced disease; eight patients with viral suppression and immunological response to HAART; and 10 patients with virological and immunological treatment failure. Eleven healthy blood donors were included as controls. Methods: The following parameters were evaluated: the production of IL-15 by peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide, Candida albicans and Mycobacterium avium complex; the ability of IL-15 to induce the secretion of IL-8 and monocyte chemotactic protein-1 (MCP-1) from HIV-positive monocytes; and the virological effect of IL-15 and IL-2 on HIV replication in mononuclear cells. Results: IL-15 production by PBMC was significantly decreased in antiretroviral-naive patients and in those with treatment failure. on the contrary, in patients with response to HAART IL-15 production was comparable to that of healthy donors. IL-15 was able to stimulate HIV-positive monocytes to produce chemokines, such as IL-8 and MCP-1, that specifically attract neutrophils and monocytes to the site of inflammation thus possibly improving immune response to pathogens during HIV infection. Finally, IL-15 had no major effect on HIV replication in vitro, while only simultaneous administration with IL-2 may induce high levels of HIV production. Conclusions: This in vitro study provides new insights in the area of IL-15-HIV interactions and suggests that IL-15 may represent a potential candidate for cytokine treatment in combination with HAART during HIV infection. (C) 2002 Lippincott Williams Wilkins.