Rheumatology 2004; 43: 398-399
Rheumatology Vol. 43 No. 3 (c) British Society for Rheumatology 2003; all rights reserved
Letter to the Editor |
Reply
University of Manchester, Rheumatism Research Centre and 1Department of Medicine, Manchester Royal Infirmary, Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, UK
Correspondence to: I. N. Bruce, University of Manchester, Rheumatism Research Centre, Central Manchester and Manchester Children's University Hospitals NHS Trust, Oxford Road, Manchester M13 9WL, UK. E-mail: Ian{at}fs1.ser.man.ac.uk
We are grateful to Dr Noël, who points out the potential issue of safety of statins, in particular whether they are actually capable of inducing the development of SLE [1]. Firstly, he draws attention to a number of case reports of patients, using a variety of statins, in whom lupus-like syndromes have been reported. It is interesting, given the large volume of prescribing of these agents in Western society, how uncommon these reactions appear to be. In many cases, as the author points out, causation has been difficult to conclusively establish [1].
There are nevertheless theoretical concerns regarding the potential immunomodulatory effects of statins and whether these may aggravate the propensity to develop SLE. In particular, these agents shift the T helper responses towards a Th2 phenotype [2]. While this would again be hypothesized to be detrimental in SLE, it is probably an oversimplification to assume that the pathological features of SLE are entirely driven by a Th2 response. For example, interferon gamma (IFN-
) appears to have important effects in the context of SLE. Jacobs et al. have demonstrated that IFN- can exacerbate lupus nephritis [3] and others have noted that a subgroup of relevant nucleosomal histone peptides stimulate IFN- production from autoreactive T cells [4]. An important effect of certain statins is to inhibit IFN--induced expression of inducible MHC class II [5]. This reduces subsequent T-cell proliferation and activation. Therefore, statins may actually have potential to attenuate certain immune responses of relevance in SLE.
There is no doubt that premature cardiovascular disease represents a major challenge in the management of SLE patients. There is also no doubt that, in all contexts in which they have been studied, statins have great potential to safely and effectively reduce the burden of cardiovascular disease. As such we recommend their use in the context of SLE where the target LDL cholesterol cannot be achieved by other means [6]. Our initial experience of prescribing statins also suggests that cholesterol reduction can be achieved without any obvious detrimental effects on the underlying SLE. It is also our own view that these agents may actually have a beneficial effect on SLE disease activity, although we acknowledge that it will take a well-designed trial to study in depth their immunomodulatory potential in SLE.
The authors have declared no conflicts of interest.
References
- Noël B. Statins and lupus erythematosus. Rheumatology 2004. In press.
- Youssef S, Stuve O, Pattarroyo JC et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002;420:78–84.[CrossRef][Medline]
- Jacobs CO, van der Meide PH, McDevitt HO. In vivo treatment of (NZBxNZW) F1 lupus-like nephritis with monoclonal antibody to gamma interferon. J Exp Med 1987;166:798–803.
[Abstract/Free Full Text] - Lu L, Kaliyaperumal A, Boumpas DT et al. Major peptide autoepitopes for nucleosome-specific T cells of human lupus. J Clin Invest 1999;104:345–55.[Web of Science][Medline]
- Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nature Med 2000;6:1399–402.[CrossRef][Web of Science][Medline]
- Wajed J, Ahmad Y, Durrington PN, Bruce IN. Prevention of cardiovascular disease in SLE. Proposed guidelines for risk factor management. Rheumatology Advance Access published July 16, 2003, 10.1093/rheumatology/keg436.
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