HIV-1 causes an imbalance in the production of interleukin-18 and its natural antagonist in HIV-infected individuals: Implications for enhanced viral replication

• Published in: The Journal of infectious diseases Vol. 201; no. 4; pp. 608 - 617
• Main Authors: Iannello, Alexandre, Boulassel, Mohamed-Rachid, Samarani, Suzanne, Tremblay, Cécile, Toma, Emil, Routy, Jean-Pierre, Ahmad, Ali
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.02.2010; University of Chicago Press; Oxford University Press
• Subjects: AIDS; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cell culture techniques; Cytokines; Enzyme linked immunosorbent assay; Fundamental and applied biological sciences. Psychology; Highly active antiretroviral therapy; HIV; HIV 1; HIV Infections - blood; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - physiology; HIV/AIDS; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Intercellular Signaling Peptides and Proteins - biosynthesis; Intercellular Signaling Peptides and Proteins - blood; Interleukin-10 - metabolism; Interleukin-18 - biosynthesis; Interleukin-18 - blood; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Macrophages; Macrophages - immunology; Macrophages - metabolism; Medical sciences; Microbiology; Miscellaneous; Transforming Growth Factor beta - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Virus Replication - immunology; Virus Replication - physiology; Viruses; Immunopathology; HIV-1 virus; Cytokine; Retroviridae; AIDS; Immune deficiency; Lentivirus; Interleukin 18; Virus; Infection; Viral disease; Replication; Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/650314

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.