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 journalArticle

Abstract

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
Volume5
Issue number3
DOIs
Publication statusPublished - May 2004

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Interleukin-2
HIV-1
Nitric Oxide
Therapeutics
Nitrites
Nitrates
Interleukin-6
Interleukin-2 Receptor alpha Subunit
Vasodilator Agents
Tachycardia
Respiratory Insufficiency
Hypotension
Appointments and Schedules
Fever
Outpatients
Tumor Necrosis Factor-alpha
Lymphocytes
Cytokines
Viruses
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Nitric oxide production in HIV-1 infected patients receiving intermittent cycles of interleukin-2 and antiretrovirals. / Torre, Donato; Speranza, Filippo; Ghezzi, Silvia; Nozza, Silvia; Tambussi, Giuseppe; Soldini, Laura; Dorigatti, Fernanda; Lazzarin, Adriano; Tambini, Roberto; Poli, Guido.

In: HIV Clinical Trials, Vol. 5, No. 3, 05.2004, p. 146-151.

Research output: Contribution to journalArticle

Torre, Donato ; Speranza, Filippo ; Ghezzi, Silvia ; Nozza, Silvia ; Tambussi, Giuseppe ; Soldini, Laura ; Dorigatti, Fernanda ; Lazzarin, Adriano ; Tambini, Roberto ; Poli, Guido. / Nitric oxide production in HIV-1 infected patients receiving intermittent cycles of interleukin-2 and antiretrovirals. In: HIV Clinical Trials. 2004 ; Vol. 5, No. 3. pp. 146-151.
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abstract = "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.",
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AU - Torre, Donato

AU - Speranza, Filippo

AU - Ghezzi, Silvia

AU - Nozza, Silvia

AU - Tambussi, Giuseppe

AU - Soldini, Laura

AU - Dorigatti, Fernanda

AU - Lazzarin, Adriano

AU - Tambini, Roberto

AU - Poli, Guido

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N2 - 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.

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KW - Nitrate/nitrite

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