The effects of atorvastatin in experimental autoimmune uveitis

P. B. Thomas, Thomas A Albini, R. K. Giri, R. F. See, M. Evans, Narsing A. Rao

Research output: Contribution to journalArticle

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Abstract

Aim: To investigate the effect of atorvastatin (Lipitor), a commonly used drug for dyslipidaemia in experimental autoimmune uveitis (EAU). Methods: 48 B10-RIII mice were immunised with human interphotoreceptor retinoid binding protein (IRBP) peptide p161-180. They were divided into three groups of 16 each and treated orally once daily for 14 days; group one received phosphate buffered saline (control group), group two received 1 mg/kg of atorvastatin (low dose group), and group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and right eyes were harvested. RNA was extracted from lymph nodes for RNase protection assay (RPA) to determine proinflammatory (IL-1α and IL-1β), Th1 (TNF-α, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from spleens for western blot to detect the expression of phosphorylated signal transducer and activator of transcription (STAT) 4 and STAT6. The severity of inflammation in enucleated eyes was graded by a masked observer. Paired t test was performed for the mean difference in histological scoring between treated groups and the immunised control group. Results: Surprisingly, atorvastatin did not modulate the immune response. The proinflammatory cytokines, IL-1α and IL-1β, and Th1 cytokines, TNF-α and IL-2, were upregulated equally in control and atorvastatin treated groups. IL-12 and Th2 cytokines were not upregulated in all three groups. Western blot analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the control and atorvastatin treated groups. Mean differences in histological scoring between treated groups and the immunised control group were not statistically significant. Conclusions: Atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription. Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.

Original languageEnglish
Pages (from-to)275-279
Number of pages5
JournalBritish Journal of Ophthalmology
Volume89
Issue number3
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Fingerprint

Uveitis
Cytokines
Interleukin-1
Interleukin-12
Control Groups
Interleukin-2
STAT4 Transcription Factor
Spleen
STAT6 Transcription Factor
Lymph Nodes
Western Blotting
Inflammation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Interleukin-5
Ribonucleases
Dyslipidemias
Atorvastatin Calcium
Interleukin-4
Interleukin-10
Phosphates

ASJC Scopus subject areas

  • Ophthalmology

Cite this

The effects of atorvastatin in experimental autoimmune uveitis. / Thomas, P. B.; Albini, Thomas A; Giri, R. K.; See, R. F.; Evans, M.; Rao, Narsing A.

In: British Journal of Ophthalmology, Vol. 89, No. 3, 01.03.2005, p. 275-279.

Research output: Contribution to journalArticle

Thomas, P. B. ; Albini, Thomas A ; Giri, R. K. ; See, R. F. ; Evans, M. ; Rao, Narsing A. / The effects of atorvastatin in experimental autoimmune uveitis. In: British Journal of Ophthalmology. 2005 ; Vol. 89, No. 3. pp. 275-279.
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AU - Rao, Narsing A.

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