Altered iron metabolism in HIV infection: Mechanisms, possible consequences, and proposals for management

Infectious Agents and Disease

Volumn 5, Issue 1, 1996, Pages 36-46

  Boelaert, Johan R ^a   Weinberg, Geoffrey A ^b   Weinberg, Eugene D ^c  

^a General Hospital St Jan   (Belgium)

^b UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^c INDIANA UNIVERSITY   (United States)

Author keywords

HIV infection; Iron chelation; Iron overload; Iron withholding defense; Iron catalyzed oxidative stress

Indexed keywords

HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; INFECTION RISK; IRON CHELATION; IRON KINETICS; IRON METABOLISM; IRON STORAGE; NONHUMAN; PRIORITY JOURNAL; REVIEW;

AIDS-RELATED OPPORTUNISTIC INFECTIONS; CHELATING AGENTS; DEFEROXAMINE; HEMOSIDEROSIS; HIV INFECTIONS; HOMEOSTASIS; HUMANS; IRON; MODELS, BIOLOGICAL; OXIDATIVE STRESS;

EID: 0030045401     PISSN: 10562044     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (100)

1. Abrams B, Duncan D, Hertz-Piccioti I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J Acq Immune Def Syndr 1993;6:949-58.
2. Alvarez-Hernandez X, Liceaga J, McKay IC, Brock JH. Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor. Lab Invest 1989;61:319-22.
3. Baruchel S, Wainberg MA. The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. J Leukoc Biol 1992;52:111-4.
4. Blumberg BS, Hann H-WL, Mildvan D, Mathur U, Lustbader E, London WT. Iron and iron binding proteins in persistent generalized lymphadenopathy and AIDS. Lancet 1984;1:347.
5. Boelaert JR, de Locht M, Van Cutsem J, Kerrels V, Cantinieaux B, Verdonck A, Van Landuyt HW, Schneider Y-J. Mucormycosis during deferoxamine is a siderophore-mediated infection: in vitro and in vivo animal studies. J Clin Invest 1993;91:1979-86.
6. Boelaert JR, Van Cutsem J, de Locht M, Schneider Y-J, Crichton RR. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int 1994;45:667-71.
7. Brittenham GM. Development of iron-chelating agents for clinical use. Blood 1992;80:569-74.
8. Byrd TF, Horwitz MA. Interferon-gamma activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest 1988;83:1457-65.
9. Byrd TF, Horwitz MA. Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes: coordinate upregulation by iron transferrin and downregulation by interferon gamma. J Clin Invest 1993;91:969-76.
10. Byrd TF, Horwitz MA. Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron: a potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. J Clin Invest 1991;88:351-7.
11. Castella A, Croxson TS, Mildvan D, Witt DH, Zalusky R. The bone marrow in AIDS. Am J Clin Pathol 1985;84:425-32.
12. Chaisson RE. Smoking cessation in patients with HIV. JAMA 1994;272:564.
13. Cinatl J, Cinatl J, Rabenau H, Gümbel HO, Kornhuber B, Doerr HW. In vitro inhibition of human cytomegalovirus replication by desferrioxamine. Antiviral Res 1994;25:73-7.
14. Clarke JR, Taylor IK, Fleming J, Nukun A, Williamson JD, Mitchell DM. The epidemiology of HIV-1 infection of the lung in AIDS patients. AIDS 1993;7:555-60.
15. Clarkson AB, Sarić M, Grady RW. Deferoxamine and eflornithine (DL-α-difluoromethylornithine) in a rat model of Pneumocystis carinii pneumonia. Antimicrob Agents Chemother 1990;34:1833-5.
16. Costagliola D, de Montalembert M, Lefrère J-J, Briand C, Rebulla P, Baruchel S, Dessi C, Fondu P, Karagiorga M, Perrimond H, Girot R. Dose of desferrioxamine and evolution of HIV-1 infection in thalassaemic patients. Br J Haematol 1994;87:849-52.
17. Crowle AJ, May MH. Inhibition of tubercle bacilli in cultured human macrophages by chloroquine used alone and in combination with streptomycin, isoniazid, pyrazinamide, and two metabolites of vitamin D. Antimicrob Agents Chemother 1990;34:2217-22.
18. de Sousa M. The immunology of iron overload. In: de Sousa M, Brock JH, eds. Iron, immunity, cancer, and inflammation. Chichester: John Wiley & Sons, 1989:247-58.
19. Dhople AM, Ibanez MA, Poirier TC. Role of iron in host-parasite interaction during chronic infections [abstract no. 863]. In: Abstract book of the 6th International Congress for Infectious Diseases. Prague, Czech Republic, 1994:277.
20. Diebold J, Tabbara W, Marche C, Audouin J, Le Tourneau A. Modifications de la moelle osseuse à divers stades de l'infection par VIH étudiées par biopsie médullaire chez quatre-vingt-cinq patients. Arch Anat Cytol Pathol 1991;39:137-46.
21. Di Franco MJ, Zaknun D, Zaknun J, Vuja E, Oswald H-P, Mayersbach P, Hunter D, Tosteson TD, Trichopoulos D, Schmitzberger R, Schönitzer D, Wachter H, Fuchs D. A prospective study of the association of serum neopterin, β2-microglobulin, and hepatitis B surface antigenemia with death in infants and children with HIV-1 disease. J Acq Immune Def Syndr 1994;7:1079-85.
22. Douvas GS, May MH, Crowle AJ. Transferrin, iron, and serum lipids enhance or inhibit Mycobacterium avium replication in human macrophages. J Infect Dis 1993;167:857-64.
23. Duchin J, Straus W, Ostroff S, Breiman R, Good R, and the M. haemophilum study group. Mycobacterium haemophilum associated with "rusty" tap water in the home - New York City [abstract no. 530]. In: Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy. New Orleans: American Society of Microbiology, 1993:216.
24. Fuchs D, Zangerle R, Artner-Dworzak E. Association between immune activation, changes of iron metabolism and anaemia in patients with HIV infection. Eur J Haematol 1993;50:90-4.
25. Gelman BB, Rodriguez-Wolf MG, Wen J, Kumar S, Campbell GR, Herzog N. Siderotic cerebral macrophages in the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1992;116:509-16.
26. Geremia GK, McCluney KW, Adler SS, Charletta DA, Hoile RD, Huckman MS, Ramsey RG. The magnetic resonance hypointense spine of AIDS. J Comput Assist Tomogr 1990;14:785-9.
27. Gherardi RK, Mhiri C, Baudrimont M, Roullet E, Berry J-P, Poirer J. Iron pigment deposits, small vessel vasculitis, and erythrophagocytosis in the muscle of human immunodeficiency virus-infected patients. Hum Pathol 1991;22:1187-94.
28. Goldin RD, Wilkins M, Dourakis S, Parkin J, Lindley R. Iron overload in multiply transfused patients who are HIV positive. J Clin Pathol 1993;46:1036-8.
29. Gordeuk V, Mukiibi J, Hasstedt ST, Samowitz W, Edwards CQ, West G, Ndambire S, Emmanuel J, Nkanza N, Chapandka Z, Randall M, Boone P, Romano P, Martell RW, Yamashita T, Effler P, Brittenham G. Iron overload in Africa: interaction between a gene and dietary iron content. N Engl J Med 1992;326:95-100.
30. Gordeuk VR, Thuma P, Brittenham G, McLaren C, Parry D, Backenstose A, Biemba G, Msiska R, Holmes L, McKinley E, Vargas L, Gilkeson R, Poltera AA. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. N Engl J Med 1992;327:1473-7.
31. Halloy V, Boelaert JR, de Locht M, Libman J, Shanzer A, Schneider Y-J. Sensitivity of different fungi/yeasts to iron depletion [Abstract]. In: Programme and Abstracts of the International Conference on Iron and Microbial Iron Chelates. Brugge, Belgium, 1993:P21.
32. Halloy V, Boelaert JR, Dromer F, Schneider Y-J. In vitro effects of DFO and of L1 on Cryptococcus neoformans [Abstract]. In: Programme and Abstracts of the International Conference on Iron and Microbial Iron Chelates. Brugge, Belgium, 1993:P20.
33. Harris CE, Biggs JC, Concannon AJ, Dodds AJ. Peripheral blood and bone marrow findings in patients with acquired immune deficiency syndrome. Pathology 1990;22:206-11.
34. Ho WZ, Harouse JM, Rando RF, Gonezol E, Srinivasan SA, Plotkin SA. Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. J Gen Virol 1990;71:97-100.
35. Holland SM, Eisenstein EM, Kuhns DB, Turner ML, Fleisher TA, Strober W, Gallin JI. Treatment of refractory disseminated nontuberculous mycobacterial infection with interferon gamma. N Engl J Med 1994;330:1348-55.
36. Israël-Biet D, Cadranel J, Even P. Human immunodeficiency virus production by alveolar lymphocytes is increased during Pneumocystis carinii pneumonia. Am Rev Respir Dis 1993;148:1308-12.
37. Jacobson ES, Petro MJ. Extracellular iron chelation in Cryptococcus neoformans. J Med Vet Mycol 1987;25:415-8.
38. Javier JJ, Fodyce-Baum MK, Beach RS, Gavancho M, Cabrejos C, Mantero-Atienza E. Antioxidant micronutrients and immune function in HIV-1 infection. FASEB Proc 1990;4:A940.
39. Karcher DS, Frost AR. The bone marrow in human immunodeficiency virus (HlV)-related disease: morphology and clinical correlation. Am J Clin Pathol 1991;95:63-71.
40. Kochan I. The role of iron in bacterial infections, with special consideration of host-tubercle bacillus interaction. Curr Top Microbiol Immunol 1973;60:1-30.
41. Koopmans PP, van der Ven AJAM, Vree TB, van der Meer JWM. Pathogenesis of hypersensitivity reactions to drugs in patients with HIV infection: allergic or toxic? AIDS 1995;9:217-22.
42. Kumar S, Campbell GA. Early cerebrovascular changes in acquired immunodeficiency syndrome (AIDS): perivascular iron pigment deposition and mural thickening of parenchymal blood vessels [Abstract]. J Neuropathol Exp Neurol 1989;48:315.
43. Lacroix C, Said G. Muscle siderosis in AIDS: a marker for macrophage dysfunction? J Neurol 1992;239:46-8.
44. Lambrecht RS, Mjanger AK. Iron availability alters extracellular and intracellular replication of Mycobacterium avium [Abstract no. U-70] In: Abstracts of the Annual Meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1993:181.
45. Lane TE, Wu-Hsieh BA, Howard DH. Iron limitation and the gamma interferon-mediated antihistoplasma state of murine macrophages. Infect Immun 1991;59:2274-8.
46. Martin JB, Easley-Shaw T, Collins C. Use of selected vitamin and mineral supplements among individuals infected with human immunodeficiency virus. J Am Diet Assoc 1991;91:476-8.
47. Murray HW. Cytokines as antimicrobial therapy for the T-cell deficient patient: prospects for treatment of nonviral opportunistic infections. Clin Infect Dis 1993;17(suppl 2):S407-13.
48. Murray HW, Granger AM, Teitelbaum RF. Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting iron. Infect Immun 1991;59:4684-6.
49. Murray MJ, Murray AB, Murray MB, Murray CJ. The adverse effect of iron repletion on the course of certain infections. Br Med J 1978;2:1113-5.
50. Nathan CF, Hibbs JB. Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 1991;3:65-70.
51. Newman SL, Gootee L, Brunner G, Deepe GS. Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J Clin Invest 1994;93:1422-9.
52. Nieman RB, Fleming J, Coker RJ, William Harris JR, Mitchell DM. The effect of cigarette smoking on the development of AIDS in HIV-1 seropositive individuals. AIDS 1993;7:705-10.
53. Nienhuis AW. Vitamin C and iron. N Engl J Med 1981;304:170-1.
54. Nottet HSLM, van Asbeck BS, de Graaf L, de Vos NM, Visser MR, Verhoef J. Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine. J Leukoc Biol 1994;56:702-7.
55. Olakanmi O, McGowan SE, Hayek MB, Britigan BE. Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. J Clin Invest 1993;91:889-99.
56. Osborne BM, Guarda LA, Butler JJ. Bone marrow biopsies in patients with the acquired immunodeficiency syndrome. Hum Pathol 1984;15:1048-53.
57. Papavassiliou P, Voyiatzaki C, Boelaert J, Soteriadou K. Effect of iron dictation on the in vitro growth of Leishmania promatigotes. J Antimicrob Chemother 1995;35:23-30.
58. Pape JW, Jean SS, Ho LJ, Hafner A, Johnson WD. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet 1993;342:268-72.
59. Perrella O, Finelli L, Munno I, Perrella A, Soscia E, Carrieri PB. Cerebrospinal fluid ferritin in human immunodeficiency virus infection: a marker of neurologic involvement? J Infect Dis 1993;168:1079-80.
60. Pettoello-Mantovani M, Casadevall A, Kollmann TR, Rubinstein A, Goldstein H. Enhancement of HIV infection by the capsular polysaccharide of Cryptococcus neoformans. Lancet 1992;339:21-3.
61. Poli G, Fauci AS. The effects of cytokines and pharmacologie agents on chronic HIV infection. AIDS Res Hum Retroviruses 1992;8:191-7.
62. Pollack S, Weaver J. Azidothymidine (AZT)-induced siderosis. Am J Hematol 1993;43:230-3.
63. Raghu B, Raghupati S, Venkatesan P. Effect of iron on the growth and siderophore production of mycobacteria. Biochem Molec Biol Intern 1993;31:341-8.
64. Riera A, Gimferrer E, Cadafalch J, Remacha A, Martin S. Prevalence of high serum and red cell ferritin levels in HIV-infected patients. Haematologica 1994;79:165-7.
65. Roux-Lombard P, Modoux C, Cruchaud A, Dayer J. Purified blood monocytes from HIV 1 infected patients produce high levels of TNF-α and IL-1. Clin Immunol Immunopathol 1989;50:374-84.
66. Sandstrom PA, Roberts B, Folks TM, Buttke TM. HIV gene expression enhances T cell susceptibility to hydrogen peroxide-induced apoptosis. AIDS Res Hum Retroviruses 1993;9:1107-13.
67. Sappey C, Boelaert JR, Legrand-Poels S, Forceille C, Favier A, Piette J. Iron chelation decreases NF-κB and HIV-1 activation due to oxidative stress. AIDS Res Hum Retroviruses 1995;11:1049-61.
68. Schreck R, Meier B, Maennel DN, Droege W, Baeuerle PA. Dithiocarbamates as potent inhibitors of nuclear factor κB activation in intact cells. J Exp Med 1992;175:1181-94.
69. Schreck R, Rieber P, Baeuerle PA. Reactive oxygen intermediates as apparently widely used messengers in the activation of NF-κB transcription factor and HIV. EMBO J 1991;10:2247-58.
70. Schwarz KB, Korba B. Desferrioxamine inhibits hepatitis B virus virion production by HepG2 cells. Hepatology 1990;12:972 (Abstract 540).
71. Shabazian LM, Woods S, Watson RR. Ethanol consumption and early retroviral infection influence liver, heart and muscle levels of iron, zinc and copper in C57BL/6 mice. Alcohol Clin Exp Res 1994;18:964-8.
72. Shanzer A, Libman J, Lytton SD, Glickstein H, Cabantchik ZI. Reversed siderophores act as antimalarial agents. Proc Natl Acad Sci USA 1991;88:6585-9.
73. Shenoy CM, Lin JH. Bone marrow findings in acquired immunodeficiency syndrome (AIDS). Am J Med Sci 1986;292:372-5.
74. Sloand E, Kumar P, Klein HG, Merritt S, Sacher R. Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection. Transfusion 1994;34:48-53.
75. Smith TW, Degirolami U, Henin D, Bolgert F, Hauw JJ. Human immunodeficiency virus (HIV) leukoencephalopathy and the microculation. J Neuropathol Exp Neurol 1990;49:357-70.
76. Sperber K, Kalb TH, Stecher VJ, Banerjee R, Mayer L. Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes. AIDS Res Hum Retroviruses 1993;9:91-8.
77. Staal FJT, Ela SW, Roederer M, Anderson MT, Herzenberg LA, Herzenberg LA. Glutathione deficiency and human immunodeficiency virus infection. Lancet 1992;339:909-12.
78. Straus WL, Ostroff SM, Jernigan DB, Kiehn TE, Sordillo EM, Armstrong D, Boone N, Schneider N, Kilburn JO, Silcox VA, LaBombardi V, Good RC. Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients. Ann Intern Med 1994;120:118-25.
79. Thompson AB, Bohling T, Heires A, Linder J, Rennard SI. Lower respiratory tract iron burden is increased in association with cigarette smoking. J Lab Clin Med 1991;117:493-9.
80. Treacy M, Lai L, Costello C, Clark A. Peripheral blood and bone marrow abnormalities in patients with HIV related disease. Br J Haematol 1987;65:289-94.
81. Van Asbeck BS, Verbrugh HA, Van Oost BA, Marx JJM, Imhof HM, Verhoef J. Listeria monocytogenes meningitis and decreased phagocytosis associated with iron overload. Br Med J 1982;284:542-4.
82. Van den Saffele JK, Boelaert JR. Zygomycosis in HIV-positive patients: a review of the literature [abstract]. In: Programme and Abstracts of the International Colloquium on Invasive Mycoses in AIDS Patients. Antwerp, Belgium: Institute for Tropical Medicine, 1994:9.
83. Voest EE, Vreugdenhil G, Marx JJM. Iron-chelating agents in non-iron overload conditions. Ann Intern Med 1994;120:490-9.
84. Vreugendhil G, Smeets M, Feelders RA, Van Eijck HG. Iron chelators may enhance erythropoiesis by increasing iron delivery to haematopoietic tissue and erythropoietin response in iron-loading anaemia. Acta Haematol 1993;89:57-60.
85. Warren S, Torti SV, Torti FM. The role of iron in the cytotoxicity of tumor necrosis factor. Lymphokine Cytokine Res 1993;12:75-80.
86. Weinberg ED. Cellular iron metabolism in health and disease. Drug Metab Rev 1990;22:531-79.
87. Weinberg ED. Roles of iron in neoplasia: promotion, prevention, and therapy. Biol Trace Elem Res 1992;34:123-40.
88. Weinberg ED. Iron and infection. Microbiol Rev 1978;42:45-66.
89. Weinberg GA. Iron chelators as novel therapeutic agents against Pneumocystis carinii. Antimicrob Agents Chemother 1994;38:997-1003.
90. 89a. Weinberg GA, Boelaert JR, Shanzer A. Further studies on the activities of iron chelators against Pneumocystis carinii [Abstract B73]. In: Program and Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1995:39.
91. Weinberg GA, Chio L-C, Queener SF. Iron chelation suppresses the growth of Toxoplasma gondii in vitro [Abstract no. 327]. In: Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1992:165.
92. Weiss G, Fuchs D, Hausen A, Reibnegger G, Werner ER, Werner-Felmayer G. Iron modulates interferon-gamma effects in the human myelomonocytic cell line THP-1. Exp Hematol 1992;20:605-10.
93. Weiss G, Werner-Felmayer G, Werner ER, Grünewald K, Wachter H, Hentze MW. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 1994;180:967-76.
94. Westendorp MO, Shatrov VA, Schultze-Osthoff A, Frank R, Kraft M, Los M, Krammer PH, Dröge W, Lehmann V. HIV-1 Tat potentiates TNF-induced NF-κB activation and cytotoxicity by altering the cellular redox state. EMBO J 1995;14:546-54.
95. Whalen C, Horsburgh CR, Hom D, Lahart C, Simberkoff M, Ellner J. Accelerated course of human immunodeficiency virus infection after tuberculosis. Am J Respir Crit Care Med 1995;151:129-35.
96. Yoshioka M, Shapshak P, Sun NCJ, Nelson SJ, Svenningsson A, Tate LG, Pardo V, Resnick L. Simultaneous detection of ferritin and HIV-1 in reactive microglia. Acta Neuropath 1992;84:297-306.
97. Youdim S. In vitro effect of iron salts and chelating agents on serum tuberculostasis. Am Rev Resp Dis 1969;99:925-31.
98. Zevin S, Link G, Grady RW, Hider RC, Peter HH, Hershko C. Origin and fate of iron mobilized by the 3-hydroxypyridin-4-one oral chelators: studies in hypertransfused rats by selective radioiron probes of reticuloendothelial and hepatocellular iron stores. Blood 1992;79:248-53.
99. Zhang Y, Nakata K, Weiden M, Rom WN. Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat. J Clin Invest 1995;95:2324-31.
100. Zon LI, Arkin C, Groopman JE. Haematologic manifestations of the human immune deficiency virus (HIV). Am J Hematol 1987;66:251-6.