TY - JOUR
T1 - HIV-1 causes an imbalance in the production of interleukin-18 and Its natural antagonist in HIV-infected individuals
T2 - Implications for enhanced viral replication
AU - Iannello, Alexandre
AU - Boulassel, Mohamed Rachid
AU - Samarani, Suzanne
AU - Tremblay, Cécile
AU - Toma, Emil
AU - Routy, Jean Pierre
AU - Ahmad, Ali
N1 - Funding Information:
Financial support: Canadian Institutes of Health Research (CIHR), Réseau SIDA et Maladies Infecteuses du Fonds de recherche en santé du Québec” (FRSQ), and a doctoral research award to I.A. from the FRSQ.
Funding Information:
patients. CIH patients who responded to HAART and had undetectable viral RNA in their plasma (!50 HIV-1 RNA copies/ mL) were categorized as CIH aviremic (CIH-A) patients. All individuals in the CIH categories and 15 individuals in the CI category had ⩾1 acquired immunodeficiency syndrome (AIDS)–defining condition. HAART consisted of different regimens that included ⩾1 nucleoside and/or nonnucleoside reverse-transcriptase inhibitors in single, dual, or triple formulations, in combination with 1 or 2 protease inhibitors or a chemokine (C-C motif) receptor 5 (CCR-5) antagonist (Vicriviroc; Schering-Plough). The date of infection of each HIV-infected individual was estimated using his/her clinical and laboratory data as well as his/her medical history, as described elsewhere [10]. We followed the guidelines proposed by the Acute HIV Infection and Early Disease Research Program sponsored by the Division of AIDS of the National Institutes of Allergy and Infectious Disease.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - Background. Concentrations of interleukin (IL)-18 increase in the circulation of human immunodeficiency virus (HIV)-infected persons. However, nothing is known concerning the regulation of IL-18-binding protein (IL-18BP), which neutralizes IL-18 in vivo. This issue is addressed in the present study. Methods. Serum samples obtained from healthy subjects and HIV-infected patients were analyzed by enzymelinked immunosorbent assay to determine their IL-18 and IL-18BP contents. Human monocyte-derived macrophages (MDMs) were infected in vitro with HIV type 1 (HIV-1), and the production of these 2 cytokines by these cells was measured. Finally, we determined the effect of IL-18 on HIV-1 replication in human cells. Results. In contrast to IL-18 levels, IL-18BP levels decreased in the serum of HIV-infected patients. This decrease resulted in enhanced levels of free IL-18 in the serum of such patients. The infection increased production of IL-18 but decreased that of IL-18BP in MDMs. IL-10 and transforming growth factor-β, concentrations of which are increased in HIV-infected persons, also decreased production of IL-18BP by human MDMs. Finally, recombinant human IL-18 enhanced HIV-1 replication in human CD4 + T cells. Conclusions. Production of IL-18 and its antagonist becomes imbalanced in HIV-1-infected persons. The infection and the cytokine milieu play a role in this decreased production. The increased biological activities of IL-18 may enhance viral replication in human CD4 + T cells.
AB - Background. Concentrations of interleukin (IL)-18 increase in the circulation of human immunodeficiency virus (HIV)-infected persons. However, nothing is known concerning the regulation of IL-18-binding protein (IL-18BP), which neutralizes IL-18 in vivo. This issue is addressed in the present study. Methods. Serum samples obtained from healthy subjects and HIV-infected patients were analyzed by enzymelinked immunosorbent assay to determine their IL-18 and IL-18BP contents. Human monocyte-derived macrophages (MDMs) were infected in vitro with HIV type 1 (HIV-1), and the production of these 2 cytokines by these cells was measured. Finally, we determined the effect of IL-18 on HIV-1 replication in human cells. Results. In contrast to IL-18 levels, IL-18BP levels decreased in the serum of HIV-infected patients. This decrease resulted in enhanced levels of free IL-18 in the serum of such patients. The infection increased production of IL-18 but decreased that of IL-18BP in MDMs. IL-10 and transforming growth factor-β, concentrations of which are increased in HIV-infected persons, also decreased production of IL-18BP by human MDMs. Finally, recombinant human IL-18 enhanced HIV-1 replication in human CD4 + T cells. Conclusions. Production of IL-18 and its antagonist becomes imbalanced in HIV-1-infected persons. The infection and the cytokine milieu play a role in this decreased production. The increased biological activities of IL-18 may enhance viral replication in human CD4 + T cells.
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U2 - 10.1086/650314
DO - 10.1086/650314
M3 - Article
C2 - 20078197
AN - SCOPUS:75749116720
VL - 201
SP - 608
EP - 617
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 4
ER -