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Published on: November 17, 2018

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Atorvastatin mediated effects depend on the activation

Eilhard Mix1, Saleh M Ibrahim, Jens Pahnke

  • 1Department of Neurology, University of Rostock, Gehlsheimer Str. 20, D-18147 Rostock, Germany.

Journal of Autoimmunity
|November 7, 2006
PubMed

Insights

Atorvastatin influences immune cell genes in experimental autoimmune encephalomyelitis (EAE) mice. These effects, partly reversed by treatment, may help predict multiple sclerosis patient response to statins.

Area of Science:

  • Immunology
  • Neuroscience
  • Pharmacology

Background:

  • Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
  • Statins, like Atorvastatin, are being investigated for their immunomodulatory effects.

Purpose of the Study:

  • To analyze the effect of Atorvastatin on gene expression in EAE.
  • To identify novel genes regulated by Atorvastatin in an autoimmune context.

Main Methods:

  • DNA microarray analysis in lymph nodes and spinal cord of EAE mice.
  • Western blot, immunohistochemistry, and flow cytometry for validation.
  • Analysis at different disease stages: onset, height, and remission.

Main Results:

  • Atorvastatin selectively influenced 14 genes in EAE mice, primarily related to immune cell function and cell-cell interactions.
  • Differential gene regulation was observed in EAE mice compared to control mice, suggesting a dependency on target cell activation status.
  • Newly identified candidate genes (COX-1, HSP-105) and known genes (ICAM-1, CD86) showed differential regulation.
  • Atorvastatin partially reversed immune cell changes in EAE mice, while similar effects were seen in healthy animals upon immunization.

Conclusions:

  • Atorvastatin modulates specific gene expression patterns in EAE.
  • Gene expression profiles and lymphocyte subpopulations may predict multiple sclerosis patient response to statins.

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