Vitamin D receptor agonists: suitable candidates as novel therapeutic options in autoimmune inflammatory myopathy

Biomed Res Int. 2014:2014:949730. doi: 10.1155/2014/949730. Epub 2014 May 7.

Abstract

The primary aim in the treatment of autoimmune inflammatory myopathies (IMs) is to recover muscle function. The presence of immune/inflammatory cell infiltrates within muscle tissues represents the common feature of different IM subtypes, albeit a correlation between muscular damage extent and inflammation degree is often lacking. Treatments for IMs are based on life-long immunosuppressive therapy, with the well known adverse effects; recovery is incomplete for many patients. More effective therapies, with reduced side-effects, are highly desirable. Vitamin D receptor (VDR) agonists emerge to retain pleiotropic anti-inflammatory properties, since they regulate innate and adaptive immunity by switching the immune response from proinflammatory T helper 1 (Th1) type to tolerogenic T helper 2 (Th2) type dominance. In skeletal muscle cells less hypercalcemic VDR ligands target powerful mediators of inflammation, such as TNF α and TNF α driven paths, without affecting immune or muscle cells viability, retaining the potentiality to counteract Th1 driven overreactivity established by the self-enhancing inflammatory loop between immune and skeletal muscle cells. This review summarizes those features of VDR agonists as candidates in future treatment of IM.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / pathology
  • Humans
  • Immune Tolerance
  • Models, Immunological
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology
  • Myositis / drug therapy*
  • Myositis / pathology
  • Receptors, Calcitriol / agonists*
  • Receptors, Calcitriol / metabolism

Substances

  • Receptors, Calcitriol