PMID- 15248139 OWN - NLM STAT- MEDLINE DCOM- 20040917 LR - 20131121 IS - 1528-4336 (Print) IS - 1528-4336 (Linking) VI - 5 IP - 3 DP - 2004 May-Jun TI - Nitric oxide production in HIV-1 infected patients receiving intermittent cycles of interleukin-2 and antiretrovirals. PG - 146-51 AB - 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 or together 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 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. 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. FAU - Torre, Donato AU - Torre D AD - Department of Infectious Diseases, General Hospital, Viale Borri 57, 21100 Varese, Italy. donatotorre@libero.it FAU - Speranza, Filippo AU - Speranza F FAU - Ghezzi, Silvia AU - Ghezzi S FAU - Nozza, Silvia AU - Nozza S FAU - Tambussi, Giuseppe AU - Tambussi G FAU - Soldini, Laura AU - Soldini L FAU - Dorigatti, Fernanda AU - Dorigatti F FAU - Lazzarin, Adriano AU - Lazzarin A FAU - Tambini, Roberto AU - Tambini R FAU - Poli, Guido AU - Poli G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - HIV Clin Trials JT - HIV clinical trials JID - 100936377 RN - 0 (Anti-HIV Agents) RN - 0 (Interleukin-2) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Adult MH - Anti-HIV Agents/*administration & dosage/adverse effects MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - HIV Infections/blood/*drug therapy/virology MH - HIV-1/drug effects/*metabolism MH - Humans MH - Interleukin-2/*administration & dosage/adverse effects/blood MH - Male MH - Nitric Oxide/*metabolism MH - Random Allocation EDAT- 2004/07/13 05:00 MHDA- 2004/09/21 05:00 CRDT- 2004/07/13 05:00 PHST- 2004/07/13 05:00 [pubmed] PHST- 2004/09/21 05:00 [medline] PHST- 2004/07/13 05:00 [entrez] AID - 10.1310/MB7D-MKTM-QPG5-HHUD [doi] PST - ppublish SO - HIV Clin Trials. 2004 May-Jun;5(3):146-51. doi: 10.1310/MB7D-MKTM-QPG5-HHUD.