Bjørn Waagsbø1,2, Asbjørn Svardal3, Thor Ueland4,5,6, Linn Landrø4,7, Olav Øktedalen8, Rolf K Berge3,9, Trude H Flo1, Pål Aukrust4,5,6,10, Jan K Damås1,2. 1. Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Trondheim, Norway. 2. Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway. 3. Department of Clinical Science, University of Bergen, Oslo, Norway. 4. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 5. Faculty of Medicine, University of Oslo, Oslo, Norway. 6. K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway. 7. Section of Dermatology, Oslo University Hospital Rikshospitalet, Oslo, Norway. 8. Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway. 9. Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. 10. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Abstract
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.
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-infectedpatients 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 MACinfection, and the release of TNF-α and IFN-γ from PBMC was decreased after stimulation with MAC-PPD in samples from HIV-infectedpatients 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-infectedpatients. Low levels of propionyl-carnitine and octanoyl-carnitine were associated with increased susceptibility to MACinfection in HIVpatients with advanced disease.
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