Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 608-617 |
| Number of pages | 10 |
| Journal | Journal of Infectious Diseases |
| Volume | 201 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 15 2010 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
Cite this
HIV-1 causes an imbalance in the production of interleukin-18 and Its natural antagonist in HIV-infected individuals : Implications for enhanced viral replication. / Iannello, Alexandre; Boulassel, Mohamed Rachid; Samarani, Suzanne; Tremblay, Cécile; Toma, Emil; Routy, Jean Pierre; Ahmad, Ali.
In: Journal of Infectious Diseases, Vol. 201, No. 4, 15.02.2010, p. 608-617.Research output: Contribution to journal › Article
}
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
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 -