Effect of N -acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial

Åkerlund, Börje; Jarstrand, Connie; Lindeke, Björn; Sönnerborg, Anders; Åkerblad, Ann‐Charlotte; Rasool, Omid

doi:10.1007/s002280050140

Cited by 93 publications

(47 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…a P b.06 compared with HNE 5 AM. increase in the CD4/CD8 ratio [8] and a slower decline of the CD4 + T cell count [9]. In the present study, we demonstrated for the first time that PTCA protected against HNE-induced cytotoxicity, possibly mediated by GSH restoration, thereby confirming the important role of GSH in HNE-induced cytotoxicity.…”

Section: Discussionsupporting

confidence: 52%

“…In T lymphocytes, thiols play an important role in regulating cell proliferation and programmed cell death. The restoration of cellular glutathione (GSH) levels is known to modulate the effect of inflammatory cytokines and increase the CD4 + cell count of HIV-infected patients [8][9][10]. Several studies demonstrated an increase in human CD4 + T lymphocyte count after supplementation with antioxidants such as N-acetyl cysteine (NAC), oxothiazolidine carboxylic acid and vitamin E among patients with immune diseases, indicating that oxidative stress can affect human CD4 + T lymphocyte survival [11,12].…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Effects of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid on 4-hydroxy-2-nonenal-induced apoptotic T cell death

Chang

McClain

Liu

et al. 2008

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 98%

Effects of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid on 4-hydroxy-2-nonenal-induced apoptotic T cell death

Chang

McClain

Liu

et al. 2008

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

“…To ameliorate these changes and their immunological consequences, we (Dröge, 1989;Dröge et al 1992) proposed treatment with a cysteine derivative such as N-acetyl-cysteine. Subsequently, the abnormal cysteine status of HIV-infected patients and simian immunodeficiency virus-infected macaques has been confirmed by other research groups (Eck et al 1991;Staal et al 1992;Hortin et al 1994;Akerlund et al 1996;Hack et al 1997;Walmsley et al 1997). Several groups also reported a significant decrease in the intracellular glutathione level of the peripheral-blood mononuclear cells from HIV-infected patients (Eck et al 1989; Roederer et al Herzenberg et al 1997;Jahoor et al 1999) and simian immunodeficiency virus-infected rhesus macaques (Eck et al 1991).…”

Section: Massive Loss Of Cysteine In Human Immunodeficiency Virus Infmentioning

confidence: 75%

Glutathione and immune function

2000

View full text Add to dashboard Cite

The immune system works best if the lymphoid cells have a delicately balanced intermediate level of glutathione. Even moderate changes in the intracellular glutathione level have profound effects on lymphocyte functions. Certain functions, such as the DNA synthetic response, are exquisitely sensitive to reactive oxygen intermediates and, therefore, are favoured by high levels of the antioxidant glutathione. Certain signal pathways, in contrast, are enhanced by oxidative conditions and favoured by low intracellular glutathione levels. The available evidence suggests that the lymphocytes from healthy human subjects have, on average, an optimal glutathione level. There is no indication that immunological functions such as resistance to infection or the response to vaccination may be enhanced in healthy human subjects by administration of glutathione or its precursor amino acid cysteine. However, immunological functions in diseases that are associated with a cysteine and glutathione deficiency may be significantly enhanced and potentially restored by cysteine supplementation. This factor has been studied most extensively in the case of human immunodeficiency virus (HIV)-infected patients who were found to experience, on average, a massive loss of S equivalent to a net loss of approximately 4 g cysteine/d. Two randomized placebo-controlled trials have shown that treatment of HIV-infected patients with N-acetyl-cysteine caused in both cases a significant increase in all immunological functions under test, including an almost complete restoration of natural killer cell activity. It remains to be tested whether cysteine supplementation may be useful also in other diseases and conditions that are associated with a low mean plasma cystine level and impaired immunological functions.

show abstract

“…Survival data for subjects who took NAC provide additional evidence supporting the finding that low GSB levels impair survival. Oral administration of NAC was recently shown to increase plasma cysteine levels in HIV-infected subjects with CD4 T cell counts above 200͞l blood (29). This 4-month study was too short to evaluate survival; however, NAC administration was shown to be associated with a significantly decreased rate of CD4 T cell loss during the trial period.…”

Section: Resultsmentioning

confidence: 98%

Glutathione deficiency is associated with impaired survival in HIV disease

Herzenberg

Rosa

Dubs

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

620

359

View full text Add to dashboard Cite

Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression. Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects. Specifically, we show that GSH deficiency in CD4 T cells from such subjects is associated with markedly decreased survival 2-3 years after baseline data collection (Kaplan-Meier and logistic regression analyses, P < 0.0001 for both analyses). This finding, supported by evidence demonstrating that oral administration of the GSH prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease. Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.

show abstract

Effect of N -acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial

Abstract: Further controlled trials with NAC are needed to determine whether it has a beneficial effect in the treatment of asymptomatic HIV-infected individuals.

Cited by 93 publications

References 19 publications

Effects of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid on 4-hydroxy-2-nonenal-induced apoptotic T cell death

Effects of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid on 4-hydroxy-2-nonenal-induced apoptotic T cell death

Glutathione and immune function

Glutathione deficiency is associated with impaired survival in HIV disease

Contact Info

Product

Resources

About