Improvement of immune functions in HIV infection by sulfur supplementation: Two randomized trials

Journal of Molecular Medicine

Volumn 78, Issue 1, 2000, Pages 55-62

  Breitkreutz, Raoul ^a   Pittack, Nicole ^b,c   Nebe, Carl Thomas ^d   Schuster, Dieter ^c   Brust, Jürgen ^c   Beichert, Matthias ^e   Hack, Volker ^a   Daniel, Volker ^f   Edler, Lutz ^a   Dröge, Wulf ^a  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b II Medizinische Klinik   (Germany)

^c HIV Schwerpunktpraxis   (Germany)

^d Institut für Klinische Chemie   (Germany)

^e UNIVERSITY OF HEIDELBERG   (Germany)

^f UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

HIV infection; Immune reconstitution in HIV infection; N Acetyl cysteine; NK cell activity; Viral load

Indexed keywords

ACETYLCYSTEINE; ANTIRETROVIRUS AGENT; CYSTEINE; PLACEBO; SERUM ALBUMIN; SULFUR AMINO ACID;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIET SUPPLEMENTATION; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNITY; MAJOR CLINICAL STUDY; MALE; NATURAL KILLER CELL; PROTEIN DEPLETION; RANDOMIZED CONTROLLED TRIAL; T LYMPHOCYTE; VIRUS LOAD;

EID: 0034024517     PISSN: 09462716     EISSN: None     Source Type: Journal    
DOI: 10.1007/s001099900073     Document Type: Article

References (53)

1. 1. Groß A, Hack V, Stahl-Hennig C, Dröge W (1996) Elevated hepatic γ-glutamylcysteine synthetase activity and abnormal sulfate levels in liver and muscle tissue may explain abnormal cysteine and glutathione levels in SIV-infected rhesus macaques. AIDS Res Hum Retroviruses 12:1639-1641
2. 2. Dröge W, Eck H-P, Näher H, Pekar U, Daniel V (1988) Abnormal amino acid concentrations in the blood of patients with acquired immune deficiency syndrome (AIDS) may contribute to the immunological defect. Biol Chem Hoppe-Seyler 369: 143-148
3. 3. Eck H-P, Gmünder H, Hartmann M, Petzoldt D, Daniel V, Dröge W (1989) Low concentrations of acid soluble thiol (cysteine) in the blood plasma of HIV-1 infected patients. Biol Chem Hoppe-Seyler 370:101-108
4. 4. Eck H-P, Stahl-Hennig C, Hunsmann G, Dröge W (1991) Metabolic disorder as an early consequence of simian immunodeficiency virus infection in rhesus macaques. Lancet 338:346-347
5. 5. Hortin GL, Landt M, Powderly WG (1994) Changes in plasma amino acid concentrations in response to HIV-1 infection. Clin Chem 40:785-789
6. 6. Roederer M, Staal FJT, Osada H, Herzenberg LA, Herzenberg LA (1991) CD4 and CD8 T cells with high intracellular glutathione levels are selectively lost as the HIV infection progresses. Int Immunol 3:933-937
7. 7. Buhl R, Holroyd K, Mastrangeli A, Cantin AM, Jaffe HA, Wells FB, Saltini C, Crystal RG (1989) Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet II: 1294-1298
8. + lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection. Blood 86:258-267
9. 9. Pirmohamed M, Williams D, Tingle MD, Barry M, Khoo SH, O'Mahony C, Wilkins EGL, Breckenridge AM, Park BK (1996) Intracellular glutathione in the peripheral blood cells of HIV-infected patients: failure to show a deficiency. AIDS 10: 501-507
10. 10. Breitkreutz R, Holm S, Pittack N, Beichert M, Babylon A, Yodoi J, Dröge W (2000) Massive loss of sulphur in HIV-infection. AIDS Res Hum Retroviruses 16:203-209
11. 11. Dröge W (1989) Metabolische Störungen bei HIV-Infektion. Project News, AIDS-Zentrum des Bundesgesundheitsamtes, Berlin, no 2, pp 4-5
12. 12. Dröge W, Eck H-P, Mihm S (1992) HIV-induced cysteine deficiency and T cell dysfunction a rationale for treatment with N-acetyl-cysteine. Immunol Today 13:211-214
13. 13. Dröge W, Groß A, Hack V, Kinscherf R, Schykowski M, Bockstette M, Mihm S, Galter D (1997) Role of cysteine and glutathione in HIV infection and cancer cachexia - therapeutic intervention with N-acetyl-cysteine (NAC). Adv Pharmacol 38:581-600
14. 14. Herzenberg LA, De Rosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW, Deresinski SC, Herzenberg LA (1997) Glutathione deficiency is associated with impaired survival in HIV disease. Proc Natl Acad Sci USA 94:1967-1972
15. 15. Akerlund B, Jarstrand C, Lindeke B, Sönnerborg A, Akerblad A-C, Rasool O (1996) Effect of N-acetylcysteine (NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial. Eur J Clin Pharmacol 50:457-461
16. 16. Olivier R (1995) Flow cytometry technique for assessing effects of N-acetylcysteine on apoptosis and cell viability of human immunodeficiency virus-infected lymphocytes. Methods Enzymol 251:270-278
17. 17. Look MP, Rockstroh JK, Rao GS, Barton S, Lemoch H, Kaiser R, Kupfer B, Sudhop T, Spengler U, Sauerbruch T (1998) Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study. Eur J Clin Invest 28:389-397
18. 18. Jahoor F, Jackson A, Gazzard B, Philips G, Sharpstone D, Frazer ME, Heird W (1999) Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate. Am J Physiol 276:E205-E211
19. 19. Walker RE, Lane HC, Boenning CM, Polis MA, Kovacs JA, Falloon J, Davey RT, Sussman H, Gabel L, Correa-Coronas R, et al (1992) The safety, pharmacokinetics, and antiviral activity of N-acetylcysteine in HIV-infected individuals. Presented at the International Conference on AIDS, abstract no MoB 0022
20. 20. Poli G, M Introna, F Zanaboni, G Peri, M Carbonari, F Aiuti, A Lazzarin, M Moroni, A Mantovani (1985) Natural killer cells in intravenous drug abusers with lymphadenopathy syndrome. Clin Exp Immunol 62:128-135
21. 21. Ullum H, Gotzsche PC, Victor J, Dickmeiss E, Skinhoj P, Pedersen BK (1995) Defective natural immunity: an early manifestation of human immunodeficiency virus infection. J Exp Med 182:789-799
22. 22. Clerici M, Stocks NI, Zajac RA, Boswell RN, Lucey DR, Via CS, Shearer GM (1989) Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. J Clin Invest 84:1892-1899
23. 23. Clerici M, Stocks NI, Zajac RA, Boswell RN, Bernstein DC, Mann DL, Shearer GM, Berzofsky JA (1989) Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals. Nature 339:383-385
24. 24. Gruters RA de, Terpstra FG, De Jong R, Van Noesel CJM, Van Lier RAW, Miedema F (1990) Selective loss of T cell functions in different stages of HIV infection. Eur J Immunol 20:1039-1044
25. 25. Rungruengthanakit K, Duerr A, Suriyanon V, Flowers L, Nagachinta T, Tansuhaj A, Kunangern D, de Boer M, Nelson KE (1996) Immune parameters among highly exposed, persistently seronegative (HEPS) Thai women. Abstracts XI International Conference on AIDS. MoA 401a 1:13 (abstract)
26. 26. Shieh TM, Carter DL, Chadwick KR, Margolick JB, Zink MC, Clements JE (1998) Role of NK cells in control of acute SIV Infection. Keystone Symposium-HIV Pathogenesis and Treatment 102:4085a (abstract)
27. 27. Ahmad A, Menezes J (1996) Defective killing activity against gp120/41 expressing human erythroleukaemic K562 cell line by monocytes and natural killer cells from HIV-infected individuals. AIDS 10:143-149
28. 28. Oliva A, Kinter AL, Vaccarezza M, Rubbert A, Catanzaro A, Moir S, Monaco J, Ehler L, Mizell S, Jackson R, Li Y, Romano JW, Fauci AS (1998) Natural killer cells from human immunodeficiency virus (HlV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. J Clin Invest 102:223-231
29. 29. Hack V, Schmid D, Breitkreutz R, Stahl-Hennig C, Drings P, Kinscherf R, Taut F, Holm E, Dröge W (1997) Cystine levels, cystine flux and protein catabolism in cancer cachexia, HIV/SIV infection and senescence. FASEB J 11:84-92
30. 30. Newsholme EA (1996) The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal Experientia 52:455-459
31. 31. Calder PC (1994) Glutamine and the immune system. Clin Nutr 13:2-8
32. 32. Moriguchi S, Miwa H, Kishino Y (1995) Glutamine supplementaion prevents the decrease of mitogen response after a treadmill exercise in rats. J Nutr Sci Vitaminol (Tokyo) 41: 115-125
33. 33. Houdijk APJ, Rijnsburger ER, Jansen J, Wesdorp RIC, Weiss JK, McCamish MA, Teerlink T, Meuwissen SGM, Haarman HJTM, Thijs LG, van Leeuwen PAM (1998) Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet 352:772-776
34. 34. Compton J (1991) Nucleic acid sequence-based amplification. Nature 350:91-92
35. 35. Bruisten S, Van Gemen B, Koppelman M, Rasch M, Van Strijp D, Schukkink R, Beyer R, Weigel H, Lens P, Huisman H (1993) Detection of HIV-1 distribution in different blood fractions by two nucleic acid amplification assays. AIDS Res Hum Retroviruses 9:259-264
36. 36. Nakamura H, De Rosa S, Roederer M, Anderson MT, Dubs JG, Yodoi J, Holmgren A, Herzenberg LA, Herzenberg LA (1996) Elevation of plasma thioredoxin levels in HIV-infected individuals. Int Immunol 8:603-611
37. 37. Hack V, Breitkreutz R, Kinscherf R, Röhrer H, Bärtsch P, Taut F, Benner A, Dröge W (1998) The redox state as a correlate of senescence and wasting and as a target for therapeutic intervention. Blood 92:59-67
38. 38. Houssiau FA, Devogelaer JP, Van Damme J, De Deuxchaisnes CN, Van Snick J (1988) IL-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 31:784-788
39. 39. Dröge W, Hohn E (1997) Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. FASEB J 11:1077-1089
40. 40. Cohen J (1997) The daunting challenge of keeping HIV suppressed. Science 277:32-33
41. 41. Grossmann Z, Polis M, Feinberg MB, Grossmann Z, Levi I, Jankelevich S, Yarchoan R, Boon J, de Wolf F, Lange JMA, Goudsmit J, Dimitrov DS, Paul WE (1999) Ongoing HIV dissemination during HAART. Nat Med 5:1099
42. 42. Morlese JF, Forrester T, Badaloo A, Del Rosario M, Frazer ME, Jahoor F (1996) Albumin kinetics in edematous and non-edematous protein-energy malnourished children. Am J Clin Nutr 64:952-959
43. 43. Jahoor F, Gazzard B, Phillips G, Sharpstone D, Delrosario M, Frazer ME, Heird W, Smith R, Jackson A (1999) The acute-phase protein response to human immunodeficiency virus infection in human subjects. Am J Physiol 276:E1092-E1098
44. 44. Hommes MJT, Romijn JA, Endert E, Sauerwein HP (1991) Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage. Am J Clin Nutr 54:311-315
45. 45. Staal FJT, Roederer M, Herzenberg LA, Herzenberg LA (1990) Intracellular thiols regulate activation of nuclear factor κB and transcription of human immunodeficiency virus. Proc Natl Acad Sci USA 87:9943-9947
46. 46. Mihm S, Ennen J, Pessara U, Kurth R, Dröge W (1991) Inhibition of HIV-1 replication and NFκB activity by cysteine and cysteine derivatives. AIDS 5:498-503
47. 47. Burgunder JM, Varriale A, Lauterburg BH (1989) Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. Eur J Clin Pharmacol 36:127-131
48. 48. Witschi A, Junker E, Schranz C, Speck RF, Lauterburg BH (1989) Supplementation of N-acetylcysteine fails to increase glutathione in lymphocytes and plasma of patients with AIDS. AIDS Res Hum Retroviruses 11:141-143
49. + cells. FASEB J 8:448-451
50. 50. Cotgreave IA (1997) N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol 38:205-227
51. 51. Traber J, Suter M, Walter P, Richter C (1992) In vivo modulation of total and mitochondrial glutathione in rat liver. Biochem Pharmacol 43:961-964
52. 52. Borgström L, Kagedal B, Paulsen O (1986) Pharmacokinetics of N-Acetylcysteine in man. Eur J Clin Pharmacol 31:217-222
53. 53. Magnusson I, Ekman L, Wangdahl M, Wahren J (1989) N-Acetyl-tyrosine and N-acetyl-L-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans. Metabolism 38:957-961