Low levels of short- and medium-chain acylcarnitines in HIV-infected patients
| Autor: | Asbjørn Svardal, Thor Ueland, Bjørn Waagsbø, Trude Helen Flo, Olav Øktedalen, Pål Aukrust, Rolf K. Berge, Jan Kristian Damås, Linn Landrø |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Clinical Biochemistry Mycobacterium avium-intracellulare infection HIV Infections Biology medicine.disease_cause Biochemistry Peripheral blood mononuclear cell Interferon-gamma 03 medical and health sciences chemistry.chemical_compound Immune system Antiretroviral Therapy Highly Active Carnitine medicine Humans Interferon gamma Longitudinal Studies Mycobacterium avium-intracellulare Infection Fatty acid metabolism Tumor Necrosis Factor-alpha General Medicine Immune dysregulation Mycobacterium avium Complex medicine.disease 030104 developmental biology chemistry Case-Control Studies Immunology Disease Progression Female Tumor necrosis factor alpha Interferon-gamma Release Tests medicine.drug |
| Zdroj: | European Journal of Clinical Investigation. 46:408-417 |
| ISSN: | 0014-2972 |
| DOI: | 10.1111/eci.12609 |
| Popis: | BACKGROUND Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection. MATERIALS AND METHODS Plasma levels of L-carnitine, its precursors, and short-, medium- and long-chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV-infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC-purified protein derivate (PPD)-induced release of TNF-α and IFN-γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines. RESULTS Plasma levels of the short-chain (e.g. propionyl-carnitine) and medium-chain (e.g. octanoyl-carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl-carnitine and octanoyl-carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl-carnitine and octanoyl-carnitine was observed prior to MAC infection, and the release of TNF-α and IFN-γ from PBMC was decreased after stimulation with MAC-PPD in samples from HIV-infected patients with low levels of propionyl-carnitine or octanoyl-carnitine. CONCLUSIONS Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV-infected patients. Low levels of propionyl-carnitine and octanoyl-carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|