Nitric oxide production in HIV-1 infected patients receiving intermittent cycles of interleukin-2 and antiretrovirals

Donato Torre, Filippo Speranza, Silvia Ghezzi, Silvia Nozza, Giuseppe Tambussi, Laura Soldini, Fernanda Dorigatti, Adriano Lazzarin, Roberto Tambini, Guido Poli

Research output: Contribution to journalArticlepeer-review


Background: Interleukin-2 (IL-2) has been investigated as an adjunct to antiretroviral therapy (ART) because of its well-demonstrated capacity of stably increasing the number of peripheral CD4+ T cell lymphocytes. However, IL-2-related adverse events (AEs), including fever, tachycardia, hypotension, and respiratory failure, are typically dose- and schedule-dependent and can potentially limit the application of IL-2 therapy in an outpatient setting. Nitric oxide (NO) is a potent vasodilator potentially responsible for some of the AEs caused by IL-2. Purpose: In this study, we determined NO production in a cohort of HIV-1 infected individuals receiving ART either alone ortogether with IL-2. Method: NO production, detected as plasma nitrate/nitrite levels by the Griess reaction, was evaluated in 3 groups of 10 individuals each. In the first group, subcutaneous (sc) administration of 12-15 million international units per day (MIU/d) of IL-2 was administered for 5 days every 8 weeks for 6 cycles together with ART; in the second group, IL-2 (6 MIU/d) was given sc for 5 days every 4 weeks for 12 cycles together with ART; whereas the third group received ART alone. Results: At baseline, the plasma nitrate/nitrite levels in the 2 groups of patients who received high and low doses of the cytokine along with ART were 28.5 ± 18.1 μmol/L and 34.2 ± 29.0 μ mol/L, respectively. These levels were comparable to those of patients treated with only ART (18.6 ± 22.4 μmol/L) and to those of 20 healthy controls (19.9 ± 5.9 μmol/L). No significant increase of plasma nitrate/nitrite levels was observed by administration of either ART or ART+IL-2. In addition, NO production was not associated significantly with different levels of tumor necrosis factor-alpha, IL-6, or soluble IL-2 receptor alpha chain in 9 individuals with WHO grade 2 and 3 AEs. Conclusion: Our results indicate that NO is unlikely to be responsible for most side effects of IL-2 therapy in HIV-1 infected individuals. Because both IL-2 and virus multiplication have been reported to independently stimulate NO production, concomitant ART may curtail NO production through inhibition of HIV-1 replication.

Original languageEnglish
Pages (from-to)146-151
Number of pages6
JournalHIV Clinical Trials
Issue number3
Publication statusPublished - May 2004


  • AIDS
  • Antiretroviral therapy
  • HIV-1 infection
  • Interleukin-2
  • Nitrate/nitrite
  • Nitric oxide

ASJC Scopus subject areas

  • Virology
  • Immunology


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