Administration of interferon (IFN)-α exacerbates reovirus type-2-triggered autoimmune insulitis in DBA/1J mice

Scand J Immunol. 2012 Oct;76(4):378-86. doi: 10.1111/j.1365-3083.2012.02754.x.

Abstract

The aim of this study is to clarify the effects of administrated interferon (IFN)-α on Reovirus type-2 (Reo-2)-triggered autoimmune insulitis. Newborn DBA/1J mice infected with Reo-2 (on day 0) showed the highest titre in the pancreas on day 5 and thereafter the titre declined. Similar viral growth curve with lower titre was found in the spleen and thymus. Insulitis with impaired glucose tolerance developed in infected mice on day 10, but not on day 5. IFN-α was produced in the blood on days 3 and 5, but not on days 7 and 10. During the virus growth phase, IFN-α positive((+)) cells were detected in some pancreatic islet cells and infiltrated dendritic cells (DCs) in interstitium. Virus antigen positive cells were detected in islet cells, but not in DCs. Administration with IFN-α (10(2) , 10(3) or 10(4) international unit) on day 7, which is the time of the disappearance of virus from the pancreas and IFN-α from the blood, exacerbated insulitis with increased glucose values compared to only infected mice. IFN-α administration at the same time of infection did not develop insulitis. In addition, IFN-α administration in uninfected mice on day 7 did not cause any damage to islet cells. The present study suggests that IFN-α may have a possibility to exacerbate Reo-2-tiggered mild insulitis.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens, Viral / immunology
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / virology
  • Blood Glucose / analysis
  • Cell Movement / drug effects
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / immunology*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / virology
  • Glucose Tolerance Test
  • Immunohistochemistry
  • Insulin / blood
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / immunology
  • Interferon-alpha / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred DBA
  • Orthoreovirus, Mammalian / immunology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Reoviridae Infections / complications
  • Reoviridae Infections / immunology*
  • Reoviridae Infections / pathology
  • Reoviridae Infections / virology
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / pathology
  • Thymus Gland / drug effects
  • Thymus Gland / immunology
  • Thymus Gland / pathology
  • Time Factors

Substances

  • Antigens, Viral
  • Blood Glucose
  • Insulin
  • Interferon-alpha
  • Recombinant Proteins