PMID- 22549432
OWN - NLM
STAT- MEDLINE
DCOM- 20121204
LR  - 20220408
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 64
IP  - 9
DP  - 2012 Sep
TI  - N-acetylcysteine reduces disease activity by blocking mammalian target of 
      rapamycin in T cells from systemic lupus erythematosus patients: a randomized, 
      double-blind, placebo-controlled trial.
PG  - 2937-46
LID - 10.1002/art.34502 [doi]
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) patients exhibit T cell 
      dysfunction, which can be regulated through mitochondrial transmembrane potential 
      (Deltapsim) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This 
      randomized, double-blind, placebo-controlled study was undertaken to examine the 
      safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC). 
      METHODS: A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 
      gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles 
      Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), 
      and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month 
      treatment period. Mitochondrial transmembrane potential and mTOR were assessed by 
      flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and 
      ethnicity were studied as controls. RESULTS: NAC up to 2.4 gm/day was tolerated 
      by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. 
      Placebo or NAC 1.2 gm/day did not influence disease activity. Considered 
      together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month (P = 
      0.0007), 2 months (P = 0.0009), 3 months (P = 0.0030), and 4 months (P = 0.0046); 
      the BILAG score after 1 month (P = 0.029) and 3 months (P = 0.009); and the FAS 
      score after 2 months (P = 0.0006) and 3 months (P = 0.005). NAC increased Deltapsim (P 
      = 0.0001) in all T cells, profoundly reduced mTOR activity (P = 0.0009), enhanced 
      apoptosis (P = 0.0004), reversed expansion of CD4-CD8- T cells (mean +/- SEM 1.35 +/- 
      0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells (P 
      = 0.045), and reduced anti-DNA production (P = 0.049). CONCLUSION: This pilot 
      study suggests that NAC safely improves lupus disease activity by blocking mTOR 
      in T lymphocytes.
CI  - Copyright (c) 2012 by the American College of Rheumatology.
FAU - Lai, Zhi-Wei
AU  - Lai ZW
AD  - State University of New York, Upstate Medical University, College of Medicine, 
      Syracuse, New York 13210, USA.
FAU - Hanczko, Robert
AU  - Hanczko R
FAU - Bonilla, Eduardo
AU  - Bonilla E
FAU - Caza, Tiffany N
AU  - Caza TN
FAU - Clair, Brandon
AU  - Clair B
FAU - Bartos, Adam
AU  - Bartos A
FAU - Miklossy, Gabriella
AU  - Miklossy G
FAU - Jimah, John
AU  - Jimah J
FAU - Doherty, Edward
AU  - Doherty E
FAU - Tily, Hajra
AU  - Tily H
FAU - Francis, Lisa
AU  - Francis L
FAU - Garcia, Ricardo
AU  - Garcia R
FAU - Dawood, Maha
AU  - Dawood M
FAU - Yu, Jianghong
AU  - Yu J
FAU - Ramos, Irene
AU  - Ramos I
FAU - Coman, Ioana
AU  - Coman I
FAU - Faraone, Stephen V
AU  - Faraone SV
FAU - Phillips, Paul E
AU  - Phillips PE
FAU - Perl, Andras
AU  - Perl A
LA  - eng
SI  - ClinicalTrials.gov/NCT00775476
GR  - R01 AI072648-03/AI/NIAID NIH HHS/United States
GR  - R01 AT004332/AT/NCCIH NIH HHS/United States
GR  - R01 AT004332-03/AT/NCCIH NIH HHS/United States
GR  - AT-004332/AT/NCCIH NIH HHS/United States
GR  - R01 AT004332-02/AT/NCCIH NIH HHS/United States
GR  - R01 AI072648-05/AI/NIAID NIH HHS/United States
GR  - R01 AI072648-02/AI/NIAID NIH HHS/United States
GR  - R01 AI072648/AI/NIAID NIH HHS/United States
GR  - R01 AI072648-04/AI/NIAID NIH HHS/United States
GR  - AI-072648/AI/NIAID NIH HHS/United States
GR  - R01 AT004332-01A1/AT/NCCIH NIH HHS/United States
GR  - U01 AR076092/AR/NIAMS NIH HHS/United States
GR  - R01 AT004332-04/AT/NCCIH NIH HHS/United States
GR  - R01 AI072648-01A2/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Placebos)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/adverse effects/pharmacology/*therapeutic use
MH  - Adult
MH  - Double-Blind Method
MH  - Female
MH  - Free Radical Scavengers/adverse effects/pharmacology/*therapeutic use
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*drug therapy/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Middle Aged
MH  - Pilot Projects
MH  - Placebos
MH  - Severity of Illness Index
MH  - T-Lymphocytes/*drug effects/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Treatment Outcome
PMC - PMC3411859
MID - NIHMS371296
EDAT- 2012/05/03 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/09/01
CRDT- 2012/05/03 06:00
PHST- 2012/05/03 06:00 [entrez]
PHST- 2012/05/03 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1002/art.34502 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2012 Sep;64(9):2937-46. doi: 10.1002/art.34502.