title: Low levels of short- and medium-chain acylcarnitines in HIV-infected patients.
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.
  
  
  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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Trondheim, Norway.|Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Waagsbø
authors.affiliation: Department of Clinical Science, University of Bergen, Oslo, Norway.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Svardal
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Section of Dermatology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Linn
authors.initials: L
authors.lastname: Landrø
authors.affiliation: Department of Infectious Diseases, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Øktedalen
authors.affiliation: Department of Clinical Science, University of Bergen, Oslo, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.affiliation: Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Trondheim, Norway.
authors.forename: Trude H
authors.initials: TH
authors.lastname: Flo
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Cancer Research and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Trondheim, Norway.|Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007371:Interferon-gamma; D059425:Interferon-gamma Release Tests; D008137:Longitudinal Studies; D008297:Male; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000097:blood* / Q000150:complications; D014409:Tumor Necrosis Factor-alpha
chemical_list: D014409:Tumor Necrosis Factor-alpha; C116917:acylcarnitine; C003223:propionylcarnitine; D007371:Interferon-gamma; C008698:octanoylcarnitine; D002331:Carnitine
keywords: Carnitine ester profile; HIV; mycobacterium avium complex