Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for...

Theiler's murine encephalomyelitis virus (TMEV) causes demyelination with inflammation of the central nervous system (CNS) in mice and is used as an animal model for multiple sclerosis (MS). Interferon-gamma inducible protein-10 kDa (IP-10) is a CXC chemokine and a chemoattractant for CXCR3+ T cells. IP-10 mRNA is expressed in the CNS during TMEV infection. However, administration of anti-IP-10 serum caused no difference in clinical signs, inflammation, demyelination, virus persistence or anti-virus antibody response in TMEV infection, while levels of virus specific and autoreactive lymphoproliferation increased. This likely reflects a difference in the pathogenesis of TMEV infection from that of two other animal models for MS, mouse hepatitis virus infection and experimental allergic encephalomyelitis (EAE), where blocking of IP-10 resulted in clinical and histological improvement with suppression of antigen specific lymphoproliferation. In this review, we compare and contrast the roles of IP-10 between the three animal models for MS, and discuss the relevance to MS patients with different clinical courses.