PMID- 18576356
OWN - NLM
STAT- MEDLINE
DCOM- 20080808
LR  - 20211020
IS  - 0004-3591 (Print)
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 7
DP  - 2008 Jul
TI  - Failure of oral atorvastatin to modulate a murine model of systemic lupus 
      erythematosus.
PG  - 2098-104
LID - 10.1002/art.23605 [doi]
AB  - OBJECTIVE: Inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 
      reductase enzyme (statins) are cholesterol-lowering drugs that have shown promise 
      as therapeutic agents in various animal models of autoimmune disease. The results 
      of initial clinical trials with statins in multiple sclerosis and rheumatoid 
      arthritis have also been encouraging. In this study, we attempted to treat a 
      widely studied murine model of spontaneous systemic lupus erythematosus (SLE) 
      with atorvastatin. METHODS: (NZB x NZW)F1 (NZB/NZW) mice received daily oral 
      doses of atorvastatin for 20 weeks. The mice were monitored weekly for survival 
      and proteinuria. Anti-double-stranded DNA (anti-dsDNA) antibody levels in sera 
      were determined by enzyme-linked immunosorbent assay (ELISA). T lymphocyte 
      cytokine production in vitro, as well as cytokine levels in vivo, were measured 
      by ELISA. T cell proliferation was assessed by thymidine incorporation assay. 
      Serum cholesterol levels were determined using a standard fluorometric assay. 
      Kidney tissue was harvested and evaluated for pathologic changes. RESULTS: In 
      NZB/NZW mice, oral atorvastatin had significant effects on T cell proliferation 
      and cytokine production in vitro. Atorvastatin also induced significant increases 
      in serum levels of interleukin-4. However, atorvastatin treatment in NZB/NZW mice 
      had no significant impact on proteinuria, survival, serum anti-dsDNA antibody and 
      cholesterol levels, or extent of renal disease. CONCLUSION: Monotherapy with oral 
      atorvastatin has no protective effects in a murine model of spontaneous SLE. The 
      efficacy of atorvastatin in human SLE remains to be determined.
FAU - Graham, Kareem L
AU  - Graham KL
AD  - Stanford University School of Medicine, Stanford, California 94305, USA.
FAU - Lee, Lowen Y
AU  - Lee LY
FAU - Higgins, John P
AU  - Higgins JP
FAU - Steinman, Lawrence
AU  - Steinman L
FAU - Utz, Paul J
AU  - Utz PJ
FAU - Ho, Peggy P
AU  - Ho PP
LA  - eng
GR  - AI10663-02/AI/NIAID NIH HHS/United States
GR  - T32 AI007290/AI/NIAID NIH HHS/United States
GR  - R01-AI-59709/AI/NIAID NIH HHS/United States
GR  - R01 AI059709/AI/NIAID NIH HHS/United States
GR  - F31 AI010663/AI/NIAID NIH HHS/United States
PT  - Journal Article
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 (Antibodies, Antinuclear)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 207137-56-2 (Interleukin-4)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antibodies, Antinuclear/blood
MH  - Atorvastatin
MH  - Cell Proliferation/*drug effects
MH  - Cholesterol/blood
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Heptanoic Acids/*administration & dosage
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage
MH  - Interleukin-4/blood
MH  - Lupus Erythematosus, Systemic/blood/*drug therapy
MH  - Mice
MH  - Mice, Inbred NZB
MH  - Pyrroles/*administration & dosage
MH  - T-Lymphocytes/*drug effects
MH  - Treatment Outcome
PMC - PMC4143381
MID - NIHMS616722
EDAT- 2008/06/26 09:00
MHDA- 2008/08/09 09:00
PMCR- 2014/08/25
CRDT- 2008/06/26 09:00
PHST- 2008/06/26 09:00 [pubmed]
PHST- 2008/08/09 09:00 [medline]
PHST- 2008/06/26 09:00 [entrez]
PHST- 2014/08/25 00:00 [pmc-release]
AID - 10.1002/art.23605 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Jul;58(7):2098-104. doi: 10.1002/art.23605.