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

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.

• Authors: Isabelle St-Amour, Mélanie Bousquet, Isabelle Paré, Janelle Drouin-Ouellet, Francesca Cicchetti, Renée Bazin, Frédéric Calon
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 9 Pg. 234 (Oct 09 2012) ISSN: 1742-2094 [Electronic] England
• PMID: 23046563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Immune System (drug effects)
• Immunoglobulins, Intravenous (therapeutic use)
• Immunologic Factors (therapeutic use)
• MPTP Poisoning (drug therapy, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Spleen (drug effects, pathology)
• T-Lymphocytes, Regulatory (drug effects)
• Tyrosine 3-Monooxygenase (metabolism)