Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction

  title={Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction},
  author={Wulf Dröge and Eggert Holm},
  journal={The FASEB Journal},
  pages={1077 - 1089}
The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called “low CG syndrome.” These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these… 

The role of oxidative imbalance in progression to AIDS: effect of the thiol supplier N-acetylcysteine.

The study suggests that the redox profile of patients may be considered a predictive marker of AIDS progression and that the acute infection and the asymptomatic phase of the disease may represent a useful period in which the combined use of antiretroviral and antioxidant drugs may be beneficial.

Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome.

  • M. Pall
  • Biology
    Medical hypotheses
  • 2000
A novel hypothesis of CFS is proposed in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and IFN-gamma, leading to increased nitric oxide levels, which may lower the HPA axis activity and be maintained by consequent lowered glucocorticoid levels.

Cysteine and glutathione in catabolic conditions and immunological dysfunction.

  • W. Dröge
  • Biology, Medicine
    Current opinion in clinical nutrition and metabolic care
  • 1999
Treatment with N-acetyl cysteine was found to increase the plasma albumin level and to ameliorate the loss of body cell mass in cancer patients and healthy individuals.

Glutamine and arginine: immunonutrients for improved health.

Clinical studies support the dietary "essentiality" of these two nutrients for improving immune responses in most immunosuppressive states associated with high rates of infection, however, the role of these nutrients in modulating the immune changes that occur with exercise in healthy athletes demands additional experiments.

Glutathione and immune function

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, and 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.

Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats

The data support the concept that HIV-1-related proteins are not merely disease markers, but rather have significant biological activity that may lead to increased oxidative stress, the stimulation of redox-sensitive pathways, and altered muscle morphologies.

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

The findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency, and N-acetyl-cysteine treatment may be recommended for patients with and without ART.

Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients

SummaryBackground HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid

Cystine and theanine: amino acids as oral immunomodulative nutrients

In mice, the preoperative administration of CT suppressed excessive inflammatory reactions associated with surgery and promoted the postoperative recovery, and in clinical studies of gastrectomized patients, CT intake suppressed excessive postoperative inflammatory reactions and induced early recovery.

Lymphocyte glutathione levels in children with cystic fibrosis.

The inverse correlation between lymphocyte GSH concentration and lung function is interpreted as a reflection of upregulation of GSH production by lung epithelial tissue in response to oxidative stress, and a potential role for supplementation with cysteine donors is interpreted.



Role of cysteine and glutathione in HIV infection and cancer cachexia: therapeutic intervention with N-acetylcysteine.

Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIV infection, and senescence

  • V. HackD. Schmid W. Dröge
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1997
Studies of plasma amino acid exchange rates in the lower extremities now show that healthy young subjects regulate their plasma cystine level in a process that may be de‐scribed as controlled constructive catabolism.

Abnormal glutathione and sulfate levels after interleukin 6 treatment and in tumor‐induced cachexia

  • V. HackA. Gross W. Dröge
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1996
The findings indicate that tumor cachexia is triggered initially by IL‐6 and is later sustained by processes driven by an abnormal cysteine metabolism in different organs and may thus be a useful therapeutic tool in clinical medicine.

Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation

Data suggests that the exposure of the normal host to cachectin is capable of inducing a pathophysiological syndrome of cachexia, anemia, and inflammation similar to that observed during inflammatory states or malignancy.

Abnormal amino-acid concentrations in the blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect.

In vitro experiments revealed that the [3H]thymidine incorporation by mitogenically stimulated murine lymphocytes and cloned T cells is inhibited by an elevation of the extracellular glutamate concentration and augmented by the addition of cysteine, suggesting the possibility that the abnormal concentrations of glutamate and cystine in the blood of HIV-infected persons may contribute to the defect in the lymphoid system.

Insulin to Impact on Protein and Amino Acid Metabolism

The cachectic cancer patient ineffectively utilizes nutrients and furthermore seems to be unable to adapt to the malnourished state as normal man does by conserving lean body mass.

[Immunological defects in septic shock. Deficiency of natural Killer cells and T-lymphocytes].

A severe decrease in NK cells and NK cell function as well as decreases in CD3 and CD4 lymphocyte subsets are present in the initial stages of septic shock.

Supplementation of N-acetylcysteine fails to increase glutathione in lymphocytes and plasma of patients with AIDS.

The failure of sulfhydryl supplementation to increase GSH suggests that the low concentrations of the tripeptide are not the result of an increased consumption secondary to an oxidant stress, but rather the consequence of a decreased rate of synthesis of GSH in HIV infection.

Immunopathogenesis of human immunodeficiency virus infection.

The phases of HIV infection are described, the effects of HIV on the various components of the immune system are investigated, and the pathogenesis of the HIV-induced lymphadenopathies and encephalopathy is analyzed, as well as the causes and mechanisms of AIDS-associated opportunistic infections and opportunistic neoplasias.