title: Nitric oxide production in HIV-1 infected patients receiving intermittent cycles of interleukin-2 and antiretrovirals.
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.
  
  
  OBJECTIVE
  In this study, we determined NO production in a cohort of HIV-1 infected individuals receiving ART either alone or together with IL-2.
  
  
  METHODS
  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 micromol/L and 34.2 +/- 29.0 micromol/L, respectively. These levels were comparable to those of patients treated with only ART (18.6 +/- 22.4 micromol/L) and to those of 20 healthy controls (19.9 +/- 5.9 micromol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, General Hospital, Viale Borri 57, 21100 Varese, Italy. donatotorre@libero.it
authors.forename: Donato
authors.initials: D
authors.lastname: Torre
authors.forename: Filippo
authors.initials: F
authors.lastname: Speranza
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghezzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Nozza
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.forename: Laura
authors.initials: L
authors.lastname: Soldini
authors.forename: Fernanda
authors.initials: F
authors.lastname: Dorigatti
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Roberto
authors.initials: R
authors.lastname: Tambini
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation
chemical_list: D019380:Anti-HIV Agents; D007376:Interleukin-2; D009569:Nitric Oxide