The Anti-Inflammatory Effects of Oral-Formulated Tacrolimus in Mice with Experimental Autoimmune Encephalomyelitis

J Korean Med Sci. 2017 Sep;32(9):1502-1507. doi: 10.3346/jkms.2017.32.9.1502.

Abstract

Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.

Keywords: EAE; Experimental Autoimmune Encephalomyelitis; FK506; Multiple Sclerosis; Neuromyelitis Optica; Tacrolimus.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomarkers / metabolism
  • CD4 Antigens / metabolism
  • Calcium-Binding Proteins / metabolism
  • Drug Compounding
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Myelin-Oligodendrocyte Glycoprotein / adverse effects
  • Severity of Illness Index
  • Spinal Cord / pathology
  • Tacrolimus / chemistry
  • Tacrolimus / therapeutic use*

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents
  • Biomarkers
  • CD4 Antigens
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Myelin-Oligodendrocyte Glycoprotein
  • Tacrolimus