Immunomodulatory effects of atorvastatin on MRL/lpr mice.
Atorvastatin
B cell
Immunomodulatory effects
MRL/lpr mice
Systemic lupus erythematosus
Journal
Advances in rheumatology (London, England)
ISSN: 2523-3106
Titre abrégé: Adv Rheumatol
Pays: England
ID NLM: 101734172
Informations de publication
Date de publication:
05 12 2022
05 12 2022
Historique:
received:
05
07
2022
accepted:
28
11
2022
entrez:
5
12
2022
pubmed:
6
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Statins have long been extensively prescribed as effective lipid-lowering agents, but statins have also been recognized as novel immunomodulators in recent years. This study was designed to investigate the immunomodulatory effects of atorvastatin on lupus-prone MRL/lpr mice. A total of 30 8-week-old female MRL/lpr mice were randomly divided into three groups and orally administered vehicle, atorvastatin orhydroxychloroquine sulfate for 11 weeks. In vivo, the effects of atorvastatin on the survival rate, renal function and spleen index in MRL/lpr mice were examined. Ex vivo, splenic B-cell proliferation was assessed by a Cell Counting Kit-8. Oral atorvastatin failed to prolong survival time, or reduce the levels of proteinuria, or serum anti-dsDNA antibody and complement proteins (C3, C4). Histologically, no significant improvement by atorvastatin was observed in the pathological manifestations of renal damage, while hydroxychloroquine sulfate significantly improved glomerular injury. Ex vivo, atorvastatin suppressed the proliferation of splenic B lymphocytes. Oral atorvastatin monotherapy had no therapeutic effects on MRL/lpr mice, whereas atorvastatin inhibited splenic B-cell proliferation in vitro, suggesting that atorvastatin has a potential therapeutic effect on systemic lupus erythematosus.
Sections du résumé
BACKGROUND
Statins have long been extensively prescribed as effective lipid-lowering agents, but statins have also been recognized as novel immunomodulators in recent years. This study was designed to investigate the immunomodulatory effects of atorvastatin on lupus-prone MRL/lpr mice.
METHODS
A total of 30 8-week-old female MRL/lpr mice were randomly divided into three groups and orally administered vehicle, atorvastatin orhydroxychloroquine sulfate for 11 weeks. In vivo, the effects of atorvastatin on the survival rate, renal function and spleen index in MRL/lpr mice were examined. Ex vivo, splenic B-cell proliferation was assessed by a Cell Counting Kit-8.
RESULTS
Oral atorvastatin failed to prolong survival time, or reduce the levels of proteinuria, or serum anti-dsDNA antibody and complement proteins (C3, C4). Histologically, no significant improvement by atorvastatin was observed in the pathological manifestations of renal damage, while hydroxychloroquine sulfate significantly improved glomerular injury. Ex vivo, atorvastatin suppressed the proliferation of splenic B lymphocytes.
CONCLUSION
Oral atorvastatin monotherapy had no therapeutic effects on MRL/lpr mice, whereas atorvastatin inhibited splenic B-cell proliferation in vitro, suggesting that atorvastatin has a potential therapeutic effect on systemic lupus erythematosus.
Identifiants
pubmed: 36471414
doi: 10.1186/s42358-022-00282-z
pii: 10.1186/s42358-022-00282-z
pmc: PMC9735199
doi:
Substances chimiques
Atorvastatin
A0JWA85V8F
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
anti-dsDNA autoantibody
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Informations de copyright
© 2022. The Author(s).
Références
Autoimmun Rev. 2016 Apr;15(4):344-53
pubmed: 26747436
Arthritis Rheum. 2001 Oct;44(10):2350-7
pubmed: 11665976
Arthritis Rheum. 2008 Jul;58(7):2098-104
pubmed: 18576356
Nat Rev Rheumatol. 2021 Sep;17(9):515-532
pubmed: 34345022
J Cachexia Sarcopenia Muscle. 2021 Apr;12(2):237-251
pubmed: 33511728
JAMA. 2017 Jun 27;317(24):2543-2544
pubmed: 28654993
J Autoimmun. 2020 Jun;110:102356
pubmed: 31810857
Autoimmun Rev. 2018 Mar;17(3):215-225
pubmed: 29353098
Lupus. 2017 Dec;26(14):1463-1472
pubmed: 28786768
J Immunol. 2004 Dec 15;173(12):7641-6
pubmed: 15585892
Nat Med. 2000 Dec;6(12):1399-402
pubmed: 11100127
Am J Kidney Dis. 2015 Jan;65(1):156-68
pubmed: 25441433
Circulation. 2019 Jun 18;139(25):e1082-e1143
pubmed: 30586774
N Engl J Med. 2011 Dec 1;365(22):2110-21
pubmed: 22129255
J Autoimmun. 2020 Aug;112:102490
pubmed: 32535128
Lupus. 2003;12(8):607-11
pubmed: 12945719
Nature. 2002 Nov 7;420(6911):78-84
pubmed: 12422218
Lupus. 2018 Feb;27(2):225-234
pubmed: 28659045
Immunol Rev. 1981;55:179-216
pubmed: 6165672
Front Immunol. 2019 Jul 17;10:1667
pubmed: 31379858
Arthritis Rheumatol. 2019 Mar;71(3):420-430
pubmed: 30294950
Autoimmun Rev. 2021 Apr;20(4):102792
pubmed: 33610751
Immunology. 2018 May;154(1):69-75
pubmed: 29392731
Am J Kidney Dis. 2003 Mar;41(3):565-70
pubmed: 12612979
South Med J. 2016 Nov;109(11):705-711
pubmed: 27812716
Ann Intern Med. 2020 Jun 2;172(11):ITC81-ITC96
pubmed: 32479157
Lancet. 2004 Jun 19;363(9426):2015-21
pubmed: 15207950
Arthritis Res Ther. 2006;8(1):R24
pubmed: 16507125
Nat Rev Immunol. 2006 May;6(5):358-70
pubmed: 16639429
Arterioscler Thromb Vasc Biol. 2021 Mar;41(3):e175-e182
pubmed: 33535790
Lancet. 2010 Nov 13;376(9753):1670-81
pubmed: 21067804