Development of an improved animal model of experimental autoimmune myositis

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14457-64. eCollection 2015.

Abstract

Multiple animal models of experimental autoimmune myositis (EAM) have been developed. However, these models vary greatly in the severity of disease and reproducibility. The goal of this study was to test whether vaccination twice with increased dose of rat myosin and pertussis toxin (PT) could induce EAM with severer disease in mice. BALB/c mice were injected with 1 mg rat myosin in 50% complete Freund's adjuvant (CFA) weekly for four times and one time of PT (EAM) or twice with 1.5 mg myosin in CFA and PT (M-EAM). In comparison with that in the CFA and PT injected controls, vaccination with rat myosin and injection PT significantly reduced the muscle strength and EMG duration, elevated serum creatine kinase levels, promoted inflammatory infiltration in the muscle tissues, leading to pathological changes in the muscle tissues, demonstrating to induce EAM. Interestingly, we found that vaccination twice with the high dose of myosin and PT prevented EAM-related gain in body weights and caused significantly less muscle strength in mice. More importantly, all of the mice receiving high dose of myosin and PT survived while 3 out of 16 mice with four times of low dose of myosin died. Finally, vaccination with high dose of myosin promoted CD4(+) and CD8(+) T cell infiltration in the muscle tissues and up-regulated MHC-I expression in the muscle tissues of mice. Hence, the new model of EAM is a time-saving, efficient and easily replicable tool for studying autoimmune myositis.

Keywords: Experimental autoimmune myositis (EAM); animal models; idiopathic inflammatory myopathies (IIM); immunosuppressive.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Chemotaxis, Leukocyte
  • Creatine Kinase, MM Form / blood
  • Disease Progression
  • Female
  • Guinea Pigs
  • Mice, Inbred BALB C
  • Muscle Strength
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myosins*
  • Nervous System Autoimmune Disease, Experimental / blood
  • Nervous System Autoimmune Disease, Experimental / chemically induced*
  • Nervous System Autoimmune Disease, Experimental / immunology
  • Nervous System Autoimmune Disease, Experimental / pathology
  • Nervous System Autoimmune Disease, Experimental / physiopathology
  • Pertussis Toxin*
  • Phenotype
  • Severity of Illness Index
  • Time Factors
  • Weight Gain

Substances

  • Biomarkers
  • Pertussis Toxin
  • Creatine Kinase, MM Form
  • Myosins