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Effect of ethanol on monocytic function in human immunodeficiency virus type 1 infection
1Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York 10029, USA.
Insights
Ethanol and its metabolites impair human immunodeficiency virus type 1 (HIV-1) infected monocyte function, reducing T-cell proliferation and cytokine production. This impairment may worsen acquired immunodeficiency syndrome (AIDS) complications.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Ethanol consumption negatively impacts immune function.
- Human immunodeficiency virus type 1 (HIV-1) infection compromises the immune system, particularly affecting monocytes/macrophages.
- Understanding the combined effects of ethanol and HIV-1 on monocytic function is crucial for managing disease progression.
Purpose of the Study:
- To investigate the impact of ethanol, acetaldehyde, and acetate on monocytic function in the context of HIV-1 infection.
- To determine if ethanol and its metabolites exacerbate HIV-1-induced defects in monocytic accessory cell function.
- To elucidate the molecular mechanisms underlying ethanol's effects on HIV-1-infected monocytes.
Main Methods:
- Utilized human macrophage hybridoma cell lines and primary human monocytes.
- Infected cell lines with HIV-1 to establish an in vitro model of HIV-1 infection.
- Treated cells with ethanol, acetaldehyde, and acetate to assess their effects on monocytic function, cytokine production, and cell surface marker expression.
Main Results:
- Ethanol and its metabolites significantly diminished monocytic accessory cell function, impairing T-cell proliferation.
- Reduced production of key pro-inflammatory cytokines (IL-1α, IL-1β, TNF-α) and increased TGF-β were observed.
- In HIV-1-infected cells, ethanol exposure led to a faster decline in accessory cell function and surface MHC class II expression.
Conclusions:
- Ethanol and its metabolites impair critical monocytic functions, including accessory cell activity and cytokine production.
- Combined ethanol exposure and HIV-1 infection accelerate the loss of monocytic function and antigen-presenting capacity.
- Ethanol-induced immunomodulation may exacerbate the immunodeficiency associated with AIDS, increasing susceptibility to opportunistic infections and disease complications.
Abstract:
We have developed a novel system to study monocytic function after human immunodeficiency virus type 1 (HIV-1) infection by infecting a series of human macrophage hybridoma cell lines with HIV-1. Since ethanol has detrimental effects on immune function, we investigated the effect of ethanol and its metabolites acetaldehyde and acetate on monocytic function by utilizing one human macrophage hybridoma cell line, clone 43, as well as primary monocytes. Pretreatment of clone 43 and primary monocytes with ethanol and its metabolites resulted in diminished accessory cell function for mitogen-, anti-CD3-, and antigen-induced T-cell proliferation. The decreased accessory cell function was associated with reduced interleukin 1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha production with loss of intracellular cytokine and mRNA production and the induction of transforming growth factor beta. In ethanol-, acetaldehyde-, and acetate-treated HIV-1-infected clone 43 cells (43HIV), there was a more rapid loss (3 days after infection) of accessory cell function at a lower infecting dose of HIV-1 than that in untreated 43HIV cells. We also observed a more rapid loss of surface class II antigen expression in the ethanol-, acetaldehyde-, and acetate-treated 43HIV cells, but no change in surface expression of CD80 or CD86. Ethanol-induced impairment of monocytic function may compound the immunologic defects of AIDS, making the infected individual more susceptible to the complications of the disease.