The Multifaceted Role of Interferon-γ in Central Nervous System Autoimmune Demyelination

ABSTRACT

Extensive research has been devoted to the study of IFN-γ function in several autoimmune diseases. Previously considered the hallmark of Th1 differentiation and pro-inflammatory responses, it has soon become evident that this pivotal cytokine plays a much more complex role than initially thought. These considerations have been particularly relevant to the understanding of the pathogenesis of autoimmune demyelination of the central nervous system (CNS). Evidence of the multifaceted effects of IFN-γ in this disease has been gathered mainly by studies in the animal model, experimental autoimmune encephalomyelitis (EAE). In this review we summarize the fundamental steps and examine the possible factors involved in the apparent dichotomy between pro-inflammatory and protective effects of IFN-γ in CNS autoimmune demyelination. A clear understanding of the heterogeneous functions of this key cytokine is paramount in order to fully explore the potential of manipulation of its pathways for the treatment of Multiple Sclerosis.

Keywords:

Multiple sclerosis, experimental autoimmune encephalomyelitis, interferon-γ, central nervous system, autoimmune demyelination.