J Rheum Dis.  2023 Jul;30(3):198-203. 10.4078/jrd.2023.0021.

Rosuvastatin treatment alone cannot alleviate lupus in murine model: a pilot study

• Baek WY
• Lee SM
• Lee SW
• Suh CH

• KMID: 2543946
• DOI: http://doi.org/10.4078/jrd.2023.0021

Abstract

Objective
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by the production of autoantibodies and high cholesterol levels. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in lupus-prone mice.
Methods
MRL/lpr mice were intraperitoneally injected with rosuvastatin (10 mg/kg, n=4) or vehicle (2% dimethyl sulfoxide, n=4) five times a week from 13 to 17 weeks of age. The serum levels of low-density lipoprotein (LDL) cholesterol and autoantibodies were measured, as well as the urine levels of albumin. Renal tissues were stained for histopathological analysis. Concentrations of key inflammatory cytokines were measured in the serum, and messenger RNA (mRNA) levels in target organs (kidney, spleen, and lymph nodes) were evaluated.
Results
Rosuvastatin treatment significantly decreased serum LDL cholesterol concentration in MRL/lpr mice. However, the clinical manifestations and autoantibody titres did not improve with rosuvastatin treatment. In addition, serum inflammatory cytokines and proteinuria did not change. Histopathological analysis of the kidneys revealed no improvement. When assessing the expression of mRNA, treatment with rosuvastatin decreased tumor necrosis alpha and interleukin-17 concentration in spleen and kidney tissue and in the kidneys and lymph nodes of MRL/lpr mice, respectively.
Conclusion
Although it can decrease inflammatory cytokines in the lymphoid organs and kidneys of MRL/lpr mice, treatment with rosuvastatin is insufficient to alleviate SLE.

Keyword

Systemic lupus erythematosus; Rosuvastatin calcium; Inbred MRL lpr mice; LDL cholesterol

Figure

• 

  Fig. 1 No change in SLE major markers by rosuvastatin treatment. (A) dsDNA antibodies, (B) ANA, (C) IL-6, and (D) LDL-cholesterol in the serum of MRL/lpr mice treated with rosuvastatin were determined using ELISA. All experiments were performed in duplicate wells (n=3~4 mice/group). The Mann–Whitney U test was used to determine differences between groups. SLE: systemic lupus erythematosus, dsDNA: anti-double-stranded DNA, ANA: antinuclear antibodies, IL-6: interleukin-6, ELISA: enzyme-linked immunosorbent assay, LDL: low-density lipoprotein. *p<0.05.

• 

  Fig. 2 Rosuvastatin did not improved LN in MRL/lpr mice. (A) Representative photographs of H&E staining (top panels) and PAS staining (bottom panels) of rosuvastatin-treated kidneys (×200). (B) Albumin content in the urine as determined using ELISA (n=4 micegroup). LN: lupus nephritis, H&E: hematoxylin and eosin, PAS: periodic acid–Schiff, ELISA: enzyme-linked immunosorbent assay.

• 

  Fig. 3 Reduction of several inflammatory cytokines in key target tissues during SLE in MRL/lpr mice. The level of pro-inflammatory cytokines in the spleen (A), kidney (B), and lymph node (C) tissues of MRL/lpr mice treated with rosuvastatin was verified at the messenger RNA level. The Mann–Whitney U test was used to determine differences between groups. TNF: tumor necrosis factor-alpha, IFN: interferon-alpha, IL-6: interleukin-6, SLE: systemic lupus erythematosus. *p<0.05.

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