HIV-1 causes an imbalance in the production of interleukin-18 and Its natural antagonist in HIV-infected individuals

Implications for enhanced viral replication

Alexandre Iannello, Mohamed Rachid Boulassel, Suzanne Samarani, Cécile Tremblay, Emil Toma, Jean Pierre Routy, Ali Ahmad

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)608-617
Number of pages10
JournalJournal of Infectious Diseases
Volume201
Issue number4
DOIs
Publication statusPublished - Feb 15 2010

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Interleukin-18
HIV-1
HIV
Interleukins
Macrophages
Virus Replication
Serum
Cytokines
T-Lymphocytes
Immunosorbents
Transforming Growth Factors
Infection
Interleukin-10
Healthy Volunteers

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 journalArticle

Iannello, Alexandre ; Boulassel, Mohamed Rachid ; Samarani, Suzanne ; Tremblay, Cécile ; Toma, Emil ; Routy, Jean Pierre ; Ahmad, Ali. / HIV-1 causes an imbalance in the production of interleukin-18 and Its natural antagonist in HIV-infected individuals : Implications for enhanced viral replication. In: Journal of Infectious Diseases. 2010 ; Vol. 201, No. 4. pp. 608-617.
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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.",
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AU - Samarani, Suzanne

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AU - Toma, Emil

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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.

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