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L-Carnitine, a Modulator of Immunometabolic Homeostasis in Subjects Infected with the Human Immunodeficiency Virus

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Carnitine Today

Abstract

The inexorable decline in the numbers of CD4 T lymphocytes, which have A a central role in the immune response to pathogens, and their association with the loss of cell-mediated immunity are major hallmarks of advancing acquired immunodeficiency syndrome (AIDS).

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References

  1. Fauci AS, Pantaleo G, Stanley S, Weissman D. Immunopathogenetic mechanisms of HIV infection. Ann Intern Med 1996; 124:654–663.

    PubMed  CAS  Google Scholar 

  2. De Simone C, Famularo G, Cifone G, Mitsuya H. HIV-1 infection and cellular metabolism. Immunol Today 1996; 17:256–258.

    Article  PubMed  Google Scholar 

  3. Famularo G, Moretti S, Marcellini S, Alesse E, De Simone C. Cellular dysmetabolism:the dark side of HIV-1 infection. J Clin Lab Immunol 1996 48:123–132.

    PubMed  CAS  Google Scholar 

  4. Deufel T. Determination of L-carnitine in biological fluids and tissues. J Clin Chem Clin Biochem 1990; 28:307–311.

    PubMed  CAS  Google Scholar 

  5. Monti D, Cossarizza A, Troiano L, Arrigoni Martelli E, Franceschi C. Immunomodulatory properties of L-acetylcarnitine on lymphocytes from young and old humans. In: De Simone C, Arrigoni Martelli E, eds. Stress, Immunity and Ageing. A Role for L-acetylcarnitine. Amsterdam: Elsevier, 1989:83–96.

    Google Scholar 

  6. De Simone C, Delogu G, Fagiola A et al. Lipids and the immune system are influenced by L-carnitine. A study in elderly subjects with cardiovascular diseases. Int J Immunother 1:267–271, 1985.

    Google Scholar 

  7. De Simone C, Ferrari M, Meli D, Midiri G, Sorice F. Reversibility by L-carnitine of immunosuppression induced by emulsion of soya bean oil, glycerol and egg lecithin. Drug Res 1982; 32:1485–1485.

    Google Scholar 

  8. Monti D, Troiano L, Tropea F et al. Apoptosis-programmed cell death: a role in the aging process? Am J Clin Nutr 1992; 55: 1208S–1214S.

    PubMed  CAS  Google Scholar 

  9. Famularo G, De Simone C, Tzantzoglou S, Trinchieri V. Apoptosis, anti-apoptotic compounds and TNF-alpha release. Immunol Today 1994; 15:495–496.

    Article  PubMed  CAS  Google Scholar 

  10. Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994; 18:S62–S67.

    Article  PubMed  Google Scholar 

  11. Majeed T, De Simone C, Famularo G, Marcellini S, Behan PO. Abnormalities of carnitine metabolism in chronic fatigue syndrome. Eur J Neurol 1995; 2:425–428.

    Article  Google Scholar 

  12. Famularo G, De Simone C, Arrigoni Martelli E, Jirillo E. Carnitine and septic shock: a review. J Endotoxin Res 1995; 2:141–147.

    Google Scholar 

  13. De Simone C, Tzantzoglou S, Jirillo E et al. Carnitine deficiency in AIDS patients. AIDS 1992; 6:203–205.

    Article  PubMed  Google Scholar 

  14. Famularo G, De Simone C. A new era for carnitine? Immunol Today 1995; 16:211–213.

    Article  PubMed  CAS  Google Scholar 

  15. Bogden JD, Baker H, Frank O et al. Micronutrient status and human immunodeficiency virus (HIV) infection. Ann NY Acad Sci 1990; 587:189–195.

    PubMed  CAS  Google Scholar 

  16. Tomaka FL, Cimoch PJ, Reiter WM et al. Prevalence of nutritional deficiencies in patients with HIV-1 infection. Int Conf AIDS 1994 (Abs. PB 0898).

    Google Scholar 

  17. Mintz M. Carnitine in human immunodeficiency virus type I/Acquired Immune Deficiency Syndrome. J Child Neurol 1995; 10:2S40–2S44.

    Google Scholar 

  18. Böhmer T, Rydning A, Solberg HE. Carnitine levels in human serum in health and disease. Clin Chem Acta 1974; 57:55–61.

    Article  Google Scholar 

  19. Tripp ME, Shug AL. Plasma carnitine concentrations in cardio-myopathy patients. Biochem Med 1984; 32:199–206.

    Article  PubMed  CAS  Google Scholar 

  20. De Simone C, Famularo G, Tzantzoglou S, Trinchieri V, Moretti S, Sorice F. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine. AIDS 1994; 8:655–660.

    Article  PubMed  Google Scholar 

  21. Herzberg VL. Human T lymphocytes require lipid as either lipopro-tein or nonesterified fatty acid for in vitro activation. Immunol Invest 1991; 20:507–513.

    Article  PubMed  CAS  Google Scholar 

  22. Hommes MJT, Romijn JA, Endert E et al. Basal fuel homeostasis in symptomatic human immunodeficiency virus infection. Clin Sei 1991; 80:359–365.

    CAS  Google Scholar 

  23. Stein TP, Nutinsky C, Condolucci D et al. Protein and energy substrate metabolism in AIDS patients. Metabolism 1990; 39:876–881.

    Article  PubMed  CAS  Google Scholar 

  24. Grunfeld C, Feingold RK. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N Engl J Med 1992; 327: 329–337.

    Article  PubMed  CAS  Google Scholar 

  25. Aguilar JJ, Anel A, Torres JM et al. Changes in lipid composition of human peripheral blood lymphocytes infected by HIV. AIDS Res Hum Retroviruses 1991; 7:761–765.

    Article  PubMed  CAS  Google Scholar 

  26. Apostolov K, Barker W, Wood CB et al. Fatty acid saturation index in peripheral blood cell membranes in AIDS patients. Lancet 1987; i:695–697.

    Google Scholar 

  27. Apostolov K, Barker W, Galpin SA. Syncytia formation in HIV-1-infected cells is associated with an increase in cellular oleic acid. FEBS Lett 1989; 250:241–244.

    Article  PubMed  CAS  Google Scholar 

  28. Klein A, Mercure L, Gordon P et al. The effect of HIV-1 infection on the lipid fatty acid content in the membrane of cultured lymphocytes. AIDS 1990; 4:865–867.

    Article  PubMed  CAS  Google Scholar 

  29. Marchalonis J. Structure and Role of Phospholipids in the Lymphocyte Plasma Membrane. New York: Marcel Dekker Inc., 1987: 171–222.

    Google Scholar 

  30. Lynn WS, Tweedale A, Cloyd MW. Human immunodeficiency virus (HIV-1) cytotoxicity: perturbation of the cell membrane and depression of phospholipid synthesis. Virology 1988; 163:43–51.

    Article  PubMed  CAS  Google Scholar 

  31. Matsuyama T, Kobayashi N, Yamamoto N. Cytokines and HIV infection: is AIDS a tumor necrosis factor disease? AIDS 1991; 5:1405–1417.

    Article  PubMed  CAS  Google Scholar 

  32. Memon RA, Feingold KR, Moser AH, Doerller W, Grunfeld C. In vivo effects of interferon-alpha and interferon-gamma on lipolysis and ketogenesis. Endocrinology 1992; 131:1695–1702.

    Article  PubMed  CAS  Google Scholar 

  33. Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs. Nature Med 1995; 1:417–422.

    Article  PubMed  CAS  Google Scholar 

  34. Dalakas MC, Leon-Monzon ME, Bernardini I, Gahl WA. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann Neurol 1994; 35:482–487.

    Article  PubMed  CAS  Google Scholar 

  35. Campos Y, Arenas J. Muscle carnitine deficiency associated with zidovudine-induced mitochondrial myopathy. Ann Neurol 1994; 36:680–681.

    Article  PubMed  CAS  Google Scholar 

  36. Semino-Mora C, Leon-Monzon ME, Dalakas MC. Effect of L-car-nitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro. Lab Invest 1994; 71: 102–112.

    CAS  Google Scholar 

  37. Semino-Mora MC, Leon-Monzon ME, Dalakas MC. Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part II: treatment with L-carnitine improves the AZT-induced changes and prevents further destruction. Lab Invest 1994; 71: 773–781.

    CAS  Google Scholar 

  38. Chattha G, Arieff AI, Cummings C, Tierney LM Jr. Lactic acidosis complicating the acquired immunodeficiency syndrome. Ann Intern Med 1993; 118:37–39.

    PubMed  CAS  Google Scholar 

  39. Freiman JP, Helfert KE, Hamrell MR, Stein DS. Hepatomegaly with severe steatosis in HIV-seropositive patients. AIDS 1993; 7:379–385.

    Article  PubMed  CAS  Google Scholar 

  40. Gopinath R, Hutcheon M, Cheema-Dhadli, Halperin M. Chronic lactc acidosis in a patient with acquired immunodeficiency syndrome and mitochondrial myopathy: biochemical studies. J Am Soc Nephrol 1992; 3:1212–1219.

    PubMed  CAS  Google Scholar 

  41. Gradon JD, Chapnick EK, Sepkowitz DV. Zidovudine-induced hepatitis. J Intern Med 1992; 231:317–318.

    Article  PubMed  CAS  Google Scholar 

  42. Lai KK, Gang DL, Zavacki JK, Cooley TP. Fulminant hepatic failure associated with 2′,3′-dideoxyinosine (ddl). Ann Intern Med 1991; 115:283–284.

    PubMed  CAS  Google Scholar 

  43. Bissuel F, Bruneel F, Habersetzer F et al. Fulminant hepatitis with severe lactic acidosis in HIV-infected patients on didanosine therapy. J Intern Med 1994; 235:367–371.

    Article  PubMed  CAS  Google Scholar 

  44. McKenzie R, Fried MW, Sallie R et al. Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B. N Engl J Med 1995; 333:1099–1105.

    Article  CAS  Google Scholar 

  45. Balistreri WF. Reye’s syndrome and its metabolic mimickers. In: Balistreri WF, Stocker JT, eds. Pediatric Hepatology. New York: Hemisphere, 1990; 183–202.

    Google Scholar 

  46. Matsuda I, Ohtani Y. Carnitine status in Reye’s and Reye-like syndrome. Pediatr Neurol 1986; 2:90–94.

    Article  PubMed  CAS  Google Scholar 

  47. Castro-Gago M, Novo I, Rodriguez-Segade S. Effects of valproic acid on the urea cycle and carnitine metabolism. Int Pediatr 1990; 5:54–57.

    Google Scholar 

  48. Simpson DM, Maltagliati M. Neurologic manifestations of HIV infection. Ann Intern Med 1994; 121:769–785.

    PubMed  CAS  Google Scholar 

  49. Faulds D, Brogden RN. Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. Drugs 1992; 44:94–116.

    Article  PubMed  CAS  Google Scholar 

  50. Whittington R, Brogden RN. Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS). Drugs 1992; 44:656–683.

    Article  PubMed  CAS  Google Scholar 

  51. Browne MJ, Mayer KN, Chapee SB et al. 2′,3′-didehydro-3′deoxy-thymidine (d4T) in patients with AIDS or AIDS related complex: a phase I trial. J Infect Dis 1993; 167:21–29.

    Article  PubMed  CAS  Google Scholar 

  52. Chen CH, Vasquez-Padua M, Cheng YC. Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol Pharmacol 1991; 39:625–628.

    PubMed  CAS  Google Scholar 

  53. Pettorossi VE, Brunetti V, Carrobi L, Delia Torre G, Grassi S. L-acetylcarnitine enhances functional muscle reinnervation. Drugs Exp Clin Res 1991; 17:119–125.

    PubMed  CAS  Google Scholar 

  54. Rampello L, Giammona G, Aleppo G, Favit A, Fiore L. Trophic action of acetyl-L-carnitine in neuronal cultures. Acta Neurol 1992; 14:15–21.

    CAS  Google Scholar 

  55. Forloni G, Angeretti N, Smiroldo S. Neuroprotective activity of acetyl-L-carnitine: studies in vitro. J Neurosci Res 1994; 37:92–96.

    Article  PubMed  CAS  Google Scholar 

  56. Rosenthal RE, Williams R, Bogaert YE, Getson PR, Fiskum G. Prevention of postischemic canine neurological injury through poten-tiation of brain energy metabolism by acetylcarnitine. Stroke 1992; 23:1312–1317.

    Article  PubMed  CAS  Google Scholar 

  57. De Angelis C, Scarfo C, Falcinelli M, Reda E, Ramacci MT, Angelucci L. Levocarnitine acetyl stimulates peripheral nerve regeneration and neuromuscular junction remodelling following sciatic nerve injury. Int J Clin Pharmacol Res 1992; 12:269–279.

    PubMed  Google Scholar 

  58. Tenconi B, Donadoni L, Germani E et al. Intraspinal degenerative atrophy caused by sciatic nerve lesions prevented by acetyl-L-carnitine. Int J Clin Pharmacol Res 1992; 12:263–267.

    PubMed  CAS  Google Scholar 

  59. Piovesan P, Pacifici L, Taglialatela G, Ramacci MT, Angelucci L. Acetylcarnitine treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following total fimbria fornix transection. Brain Res 1994; 633:77–82.

    Article  PubMed  CAS  Google Scholar 

  60. De Simone R, Ramacci MT, Aloe L. Effect of acetyl-L-carnitine on forebrain cholinergic neurons of developing rats. Int J Dev Neurosci 1991; 9:39–46.

    Article  PubMed  Google Scholar 

  61. Taglialatela G, Angelucci L, Ramacci MT, Werrbach Perez K, Jackson GR, Perez Polo JR. Stimulation of nerve growth factor receptors in PC12 cells by acetyl-L-carnitine. Biochem Pharmacol 1992; 44:577–585.

    Article  PubMed  CAS  Google Scholar 

  62. Taglialatela G, Navarra G, Cruciani R, Ramacci MT, Alema GS, Angelucci L. Acetyl-L-carnitine increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp Gerontol 1994; 29:55–66.

    Article  PubMed  CAS  Google Scholar 

  63. Castorina M, Ferraris L. Acetyl-L-carnitine affects aged brain receptorial system in rodents. Life Sci 1994; 54:1205–1214.

    Article  PubMed  CAS  Google Scholar 

  64. Gadaleta MN, Petruzzella V, Renis M et al. Reduced transcription of mitochondrial DNA in the senescent rat: tissue dependence and effect of L-camitine. Eur J Biochem 1990; 187:501–506.

    Article  PubMed  CAS  Google Scholar 

  65. Villa RF, Turpenoja L, Benzi G et al. Action of L-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum. Neurochem Res 1988; 13:509–516.

    Article  Google Scholar 

  66. Villa RF, Gorrini A. Action of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus and striatum during aging. Neurochem Res 1991; 16:1125–1132.

    Article  PubMed  CAS  Google Scholar 

  67. Famularo G, Moretti S, Marcellini S et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogs. AIDS 1997 (in press).

    Google Scholar 

  68. Famularo G, Matricardi F, De Simone C. Carnitine deficiency: primary and secondary syndromes. In: De Simone C, Famularo G, eds. Carnitine Today. Austin: RG Landes 1997; 119–172.

    Google Scholar 

  69. De Simone C, Tzantzoglou S, Famularo G et al. High-dose L-car-nitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol Immunotoxicol 1993; 15:1–12.

    Article  PubMed  Google Scholar 

  70. Gougeon ML, Lecoeur H, Dulioust A et al. Programmed cell death in peripheral lymphocytes from HIV-infected persons. J Immunol 1996; 156:3509–3520.

    PubMed  CAS  Google Scholar 

  71. Spiegel S, Foster D, Kolesnick R. Signal transduction through lipid second messengers. Curr Op Biol 1996; 8:159–167.

    Article  CAS  Google Scholar 

  72. Cifone MG, De Maria R, Roncaioli P et al. Apoptotic signaling through CD95 (Fas/APO-1) activates an acidic sphingomyelinase. J Exp Med 1994; 177:1547–1552.

    Article  Google Scholar 

  73. Cifone MG, Roncaioli P, De Maria R et al. Multiple pathways originate at the Fas/APO-1 (CD95) receptor: sequential involvement of phosphatidylcholine-specific phospholipase C and acidic sphingo-myelinase in the propagation of the apoptotic signal. EMBO J 1995; 14:5859–5868.

    PubMed  CAS  Google Scholar 

  74. Van Veldhoven PP, Matthews JJ, Bolognesi DP, Bell RM. Changes in bioactive lipids alkylacylglycerol and ceramide occur in HIV-in-fected cells. Biochem Biophys Res Commun 1992; 187:209–216.

    Article  PubMed  Google Scholar 

  75. Rivas CI, Golde DW, Vera JC, Kolesnick RN. Involvement of the sphingomyelin pathway in TNF signaling for HIV production in chronically infected HL-60 cells. Blood 1993; 83:2191–2197.

    Google Scholar 

  76. Papp B, Zhang D, Groopman JE, Byrn RA. Stimulation of human immunodeficiency virus type I expression by ceramide. AIDS Res Hum Retroviruses 1994; 10:775–780.

    PubMed  CAS  Google Scholar 

  77. De Simone C, Cifone MG, Roncaioli P et al. Ceramide, AIDS and long-term survivors. Immunol Today 1996; 17:48–49.

    Article  PubMed  Google Scholar 

  78. De Simone C, Cifone MG, Di Marzio L et al. Cell-associated ceramide in HIV-1-infected subjects. AIDS 1996; 10:675–676.

    Article  PubMed  Google Scholar 

  79. Di Marzio L, Alesse E, Roncaioli P et al. Influence of L-carnitine on Fas crosslinking-induced apoptosis and ceramide generation in T cell lines: Correlation with its effects on purified acidic and neutral sphingomyelinase in vitro. Proceedings of The American Association of Physicians (in press).

    Google Scholar 

  80. Alesse E, Di Marzio L, Roncaioli P et al. Effect of L-carnitine on Fas-induced apoptosis and sphingomyelinase activity in human T cell lines. In: De Simone C, Famularo G, eds. Carnitine Today. Austin: G Landes 1997; 259–270.

    Google Scholar 

  81. Cifone MG, Alesse E, Di Marzio L et al. Effect of L-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients. Proceedings of The American Association of Physicians (in press).

    Google Scholar 

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De Simone, C., Moretti, S., Marcellini, S., Trinchieri, V., Boschini, A., Famularo, G. (1997). L-Carnitine, a Modulator of Immunometabolic Homeostasis in Subjects Infected with the Human Immunodeficiency Virus. In: Carnitine Today. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6005-0_11

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  • DOI: https://doi.org/10.1007/978-1-4615-6005-0_11

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