Interleukin-15 modulates interferon-gamma and beta-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-gamma production from purified CD4(+) and CD8(+) T cells, and the ability of IL-15 to stimulate the beta-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-gamma production, also in patients receiving HAART. Finally, IL-15 had positive effects on RANTES, MIP-1alpha, and MIP-1beta 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-gamma production and beta-chemokine release. These data about functional properties of IL-15 could provide new implications for immune-based therapies in HIV infection.
Forcina
Gabriele
G
Department of Infectious and Tropical Diseases, La Sapienza University, Policlinico Umberto I, Viale Regina Elena 331, 00161 Rome, Italy. gab.forcina@inwind.it
D'Ettorre
Gabriella
G
Mastroianni
Claudio M
CM
Carnevalini
Martina
M
Scorzolini
Laura
L
Ceccarelli
Giancarlo
G
D'Agostino
Claudia
C
Lichtner
Miriam
M
Massetti
Anna P
AP
Vullo
Vincenzo
V
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000096:biosynthesis*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000502:physiology*; D008297:Male; D008875:Middle Aged
D019742:Chemokines, CC; D019409:Interleukin-15; D007371:Interferon-gamma