Use of atorvastatin as an anti-inflammatory treatment in Crohn's disease

Abstract

Background and purpose: Experimental and clinical investigations have revealed that statins can downregulate both acute and chronic inflammatory processes. Whether statins express anti-inflammatory activities in the treatment of Crohn's disease is unknown.

Experimental approach: Ten patients were given 80 mg atorvastatin once daily for 13 weeks and then followed up for 8 weeks after the treatment. The anti-inflammatory effects of statin were assessed by measuring levels of plasma C-reactive protein (CRP), soluble (s) CD14, tumour necrosis factor (TNF)-alpha, sTNFRI and II, CCL2 and 8 and the mucosal inflammation by faecal calprotectin. Circulating monocytes were subgrouped and their chemokine receptor expression of CCR2 and CX(3)CR1 were analysed.

Key results: In 8 of 10 patients, atorvastatin treatment reduced CRP (P=0.008) and sTNFRII (P=0.064). A slight decrease in plasma levels of sCD14, TNF-alpha and sTNFRI was observed in 7/10 patients and faecal calprotectin was reduced in 8/10 patients. We also observed that the treatment diminished expression of CCR2 and CX(3)CR1 on monocyte populations (P=0.014). At the follow-up visit, 8 weeks after the atorvastatin treatment was terminated, CRP levels had returned to those seen before the treatment.

Conclusions and implications: Our findings imply that atorvastatin therapy reduces inflammation in patients with Crohn's disease and, therefore, encourage further investigations of statin-mediated protective effects in inflammatory bowel diseases.

Figure 1

C-reactive protein (CRP) levels of 10 patients receiving 80 mg atorvastatin once daily for 13 weeks (grey area) and then followed up 8 weeks after the termination of treatment.

Figure 2

Peripheral monocytes analysed by flow cytometry. Leukocytes initially separated in bivariate plot of forward scatter (FSC) vs side scatter (SSC) to identify monocytes and ellipse gated in R1. Then gated monocytes were subdivided by expression of CD14, CD16 and CD56. Subpopulations are defined as CD14^highCD16⁻, region 2; CD14^highCD16⁺, region 3; CD14^lowCD16⁺, region 5 and CD14⁺CD56⁺, region 9.

Figure 3

Crohn's disease activity index (CDAI) of 10 patients receiving 80 mg atorvastatin once daily for 13 weeks (grey area) and then followed up 8 weeks after the termination of treatment.