Tumor necrosis factor alpha, interleukin 2, and soluble interleukin 2 receptor levels in human immunodeficiency virus type 1-infected individuals receiving intermittent cycles of interleukin 2.
HIV-infected individuals with 200-500 CD4(+) T cell/microl were enrolled in a controlled study of three interleukin 2 (IL-2) plus antiretroviral therapy (ART) regimens: (1) continuous intravenous administration of 12 million international units (MIU) of IL-2 followed by subcutaneous high-dose IL-2 (7.5 MIU, twice daily) for 5 days every 8 weeks; (2) high-dose subcutaneous IL-2 for 5 days every 8 weeks; (3) low-dose (3 MIU, twice daily) subcutaneous IL-2 for 5 days every 4 weeks; and (4) ART alone. Serum concentrations of IL-2, soluble IL-2 receptor (sIL-2R), tumor necrosis factor alpha (TNF-alpha), and IL-6 were determined. A progressive decrease over time of the circulating levels of IL-2 was observed in individuals receiving the highest doses of IL-2, but not in those belonging to the low-dose arm. Conversely, increased levels of sIL-2R were observed in all cytokine-treated individuals. The levels of TNF-alpha increased in the high-dose IL-2 regimens, but decreased in individuals receiving low-dose IL-2. IL-2-related toxicity was significantly correlated to the peak IL-2 serum levels, and was substantially lower in those individuals receiving low-dose IL-2. In conclusion, intermittent IL-2 administration causes the elevation of peripheral CD4(+) T cells, but also a profound cytokine response and systemic toxicity. The latter was correlated to the peak serum level of IL-2, but not to those of TNF-alpha and IL-6.
Fortis
Claudio
C
Division of Infectious Diseases, San Raffaele Scientific Institute, 20127 Milan, Italy. fortis.claudio@hsr.it
Soldini
Laura
L
Ghezzi
Silvia
S
Colombo
Stefania
S
Tambussi
Giuseppe
G
Vicenzi
Elisa
E
Gianotti
Nicola
N
Nozza
Silvia
S
Veglia
Fabrizio
F
Murone
Michelangelo
M
Lazzarin
Adriano
A
Poli
Guido
G
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015375:Receptors, Interleukin-2 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D019380:Anti-HIV Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha