Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson's disease

J Neuroinflammation. 2012 Oct 9;9:234. doi: 10.1186/1742-2094-9-234.

Abstract

Intravenous immunoglobulin (IVIg) is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson's disease (PD), we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg) at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4(+)/CD8(+) ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P < 0.01), as well as 33% and 40% reductions in the number of nigral dopaminergic neurons (P < 0.001) in controls and IVIg-treated mice, respectively. Two-way analyses of variance further revealed lower striatal tyrosine hydroxylase protein levels, striatal homovanillic acid concentrations and nigral dopaminergic neurons (P < 0.05) in IVIg-treated animals. Collectively, our results fail to support a neurorestorative effect of IVIg on the nigrostriatal system in the MPTP-treated mice and even suggest a trend toward a detrimental effect of IVIg on the dopaminergic system. These preclinical data underscore the need to proceed with caution before initiating clinical trials of IVIg in PD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Weight / drug effects
  • Brain / pathology
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immune System / drug effects*
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • MPTP Poisoning* / drug therapy
  • MPTP Poisoning* / immunology
  • MPTP Poisoning* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Spleen / drug effects
  • Spleen / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • CD4 Antigens
  • CD8 Antigens
  • Dopamine Plasma Membrane Transport Proteins
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Tyrosine 3-Monooxygenase
  • Dopamine