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Papaverine hydrochloride: effects on HIV replication and T-lymphocyte cell function
M Nokta1, T Albrecht, R Pollard
1Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Immunopharmacology
|September 1, 1993
Summary
Papaverine hydrochloride (PAP) significantly inhibits human immunodeficiency virus (HIV) replication and enhances interferon-gamma production in T cells. This antiviral compound shows potential for therapeutic applications in viral infections.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Papaverine hydrochloride (PAP) is known to inhibit cytomegalovirus and measles virus replication.
- The antiviral and immunomodulatory effects of PAP on human immunodeficiency virus (HIV) and T lymphocytes require further investigation.
Purpose of the Study:
- To evaluate the efficacy of PAP in inhibiting HIV replication in MT4 cells.
- To assess the impact of PAP on T lymphocyte function, including proliferation and cytokine production.
Main Methods:
- MT4 cells infected with HIV were treated with varying concentrations of PAP.
- HIV replication was quantified using reverse transcriptase activity and p24 antigen levels.
- Peripheral blood mononuclear cells (PBMC) were stimulated with mitogens or antigens in the presence of PAP.
- Proliferative responses and cytokine production (IFN-gamma, IL-2) were measured.
Main Results:
- PAP demonstrated significant inhibition of HIV replication, exceeding 99% at 30 microM.
- The 50% effective dose (ED50) for HIV inhibition was 5.8 microM.
- PAP enhanced interferon-gamma production induced by phytohemagglutinin and cytomegalovirus antigen at low doses (1-10 microM).
- Higher PAP concentrations exhibited inhibitory effects on T cell proliferation and cytokine production.
Conclusions:
- PAP is a potent inhibitor of HIV replication, with a mechanism independent of cAMP levels or direct reverse transcriptase activity.
- PAP exhibits immunomodulatory effects, enhancing IFN-gamma production at specific concentrations.
- Further research is warranted to explore PAP's therapeutic potential against viral infections and its impact on immune function.