Interleukin-15 in HIV infection: immunological and virological interactions in antiretroviral-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.


METHODS
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.
d'Ettorre
Gabriella
G
Department of Infectious and Tropical Diseases, La Sapienza University of Rome, Italy.
Forcina
Gabriele
G
Lichtner
Miriam
M
Mengoni
Fabio
F
D'Agostino
Claudia
C
Massetti
Anna P
AP
Mastroianni
Claudio M
CM
Vullo
Vincenzo
V
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001782:Blood Donors; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D018932:Chemokine CCL2; D019409:Interleukin-15; D007376:Interleukin-2; D016209:Interleukin-8